Search

Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for the hydraulic inflation of a lumen. However, the depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements of hydrostatic lumen pressure and junctional tension with modeling enabled us to explain lumen morphologies from the pressure-tension force balance. Tight junctions promote lumen inflation by decreasing cortical tension via the inhibition of myosin. In addition, our results suggest that excess apical area contributes to lumen opening. Overall, we provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape. [Display omitted] • Depletion of ZO scaffold causes lumen collapse and apical membrane folding • The claudin permeability barrier is not necessary for hydraulic lumen inflation • Tight junctions promote lumen inflation by decreasing cortical tension • Lumen shape controlled by pressure-tension force balance and apical area constraints Mukenhirn et al. show that epithelial cells use tight junctions to control lumen shape, and the depletion of the tight junction scaffold leads to lumen collapse and increased cortical tension. Claudin-depleted MDCK-II cysts maintain lumen pressure and shape despite high ion permeability. [ABSTRACT FROM AUTHOR]

Mixtures of filaments and molecular motors form active materials with diverse dynamical behaviors that vary based on their constituents' molecular properties. To develop a multiscale of these materials, we map the nonequilibrium phase diagram of microtubules and tip-accumulating kinesin-4 molecular motors. We find that kinesin-4 can drive either global contractions or turbulentlike extensile dynamics, depending on the concentrations of both microtubules and a bundling agent. We also observe a range of spatially heterogeneous nonequilibrium phases, including finite-sized radial asters, 1D wormlike chains, extended 2D bilayers, and system-spanning 3D active foams. Finally, we describe intricate kinetic pathways that yield microphase separated structures and arise from the inherent frustration between the orientational order of filamentous microtubules and the positional order of tip-accumulating molecular motors. Our work reveals a range of novel active states. It also shows that the form of active stresses is not solely dictated by the properties of individual motors and filaments, but is also contingent on the constituent concentrations and spatial arrangement of motors on the filaments.

We propose and study a simple, physical model for phagocytosis, i.e. the active, actin-mediated uptake of micron-sized particles by biological cells. The cell is described by the phase field method and the driving mechanisms of uptake are actin ratcheting, modeled by a dynamic vector field, as well as cell-particle adhesion due to receptor-ligand binding. We first test the modeling framework for the symmetric situation of a spherical cell engulfing a fixed spherical particle. We then exemplify its versatility by studying various asymmetric situations like different particle shapes and orientations, as well as the simultaneous uptake of two particles. In addition, we perform a perturbation theory of a slightly modified model version in the symmetric setting, allowing to derive a reduced model, shedding light on the effective driving forces and being easier to solve. This work is meant as a first step in describing phagocytosis and we discuss several effects that are amenable to future modeling within the same framework.

Quantum neurobiology is concerned with potential quantum effects operating in the brain and the application of quantum information science to neuroscience problems, the latter of which is the main focus of the current paper. The human brain is fundamentally a multiscalar problem, with complex behavior spanning nine orders of magnitude-scale tiers from the atomic and cellular level to brain networks and the central nervous system. In this review, we discuss a new generation of bio-inspired quantum technologies in the emerging field of quantum neurobiology and present a novel physics-inspired theory of neural signaling (AdS/Brain (anti-de Sitter space)). Three tiers of quantum information science-directed neurobiology applications can be identified. First are those that interpret empirical data from neural imaging modalities (EEG, MRI, CT, PET scans), protein folding, and genomics with wavefunctions and quantum machine learning. Second are those that develop neural dynamics as a broad approach to quantum neurobiology, consisting of superpositioned data modeling evaluated with quantum probability, neural field theories, filamentary signaling, and quantum nanoscience. Third is neuroscience physics interpretations of foundational physics findings in the context of neurobiology. The benefit of this work is the possibility of an improved understanding of the resolution of neuropathologies such as Alzheimer’s disease.

We formulate an active-gel theory for multicellular migration in the extra-cellular matrix (ECM). The cells are modeled as an active, polar solvent, and the ECM as a viscoelastic solid. Our theory enables to analyze the dynamic reciprocity between the migrating cells and their environment in terms of distinct relative forces and alignment mechanisms. We analyze the linear stability of polar cells migrating homogeneously in the ECM. Our theory predicts that, as a consequence of cell-matrix alignment, contractile cells migrate homogeneously for small wave vectors, while sufficiently extensile cells migrate in domains. Homogeneous cell migration of both extensile and contractile cells may be unstable for larger wave vectors, due to active forces and the alignment of cells with their concentration gradient. These mechanisms are stabilized by cellular alignment to the migration flow and matrix stiffness. They are expected to be suppressed entirely for rigid matrices with elastic moduli of order 10Â kPa. Our theory should be useful in analyzing multicellular migration and ECM patterning at the mesoscopic scale. [ABSTRACT FROM AUTHOR]

The volume of the cell nucleus varies across cell types and species and is commonly thought to be determined by the size of the genome and degree of chromatin compaction. However, this notion has been challenged over the years by much experimental evidence. Here, we consider the physical condition of mechanical force balance as a determining condition of the nuclear volume and use quantitative, order-of-magnitude analysis to estimate the forces from different sources of nuclear and cytoplasmic pressure. Our estimates suggest that the dominant pressure within the nucleus and cytoplasm of nonstriated muscle cells originates from the osmotic pressure of proteins and RNA molecules that are localized to the nucleus or cytoplasm by out-of-equilibrium, active nucleocytoplasmic transport rather than from chromatin or its associated ions. This motivates us to formulate a physical model for the ratio of the cell and nuclear volumes in which osmotic pressures of localized proteins determine the relative volumes. In accordance with unexplained observations that are a century old, our model predicts that the ratio of the cell and nuclear volumes is a constant, robust to a wide variety of biochemical and biophysical manipulations, and is changed only if gene expression or nucleocytoplasmic transport is modulated. [ABSTRACT FROM AUTHOR]

Quantum neurobiology is concerned with potential quantum effects operating in the brain and the application of quantum information science to neuroscience problems, the latter of which is the main focus of the current paper. The human brain is fundamentally a multiscalar problem, with complex behavior spanning nine orders of magnitude-scale tiers from the atomic and cellular level to brain networks and the central nervous system. In this review, we discuss a new generation of bio-inspired quantum technologies in the emerging field of quantum neurobiology and present a novel physics-inspired theory of neural signaling (AdS/Brain (anti-de Sitter space)). Three tiers of quantum information science-directed neurobiology applications can be identified. First are those that interpret empirical data from neural imaging modalities (EEG, MRI, CT, PET scans), protein folding, and genomics with wavefunctions and quantum machine learning. Second are those that develop neural dynamics as a broad approach to quantum neurobiology, consisting of superpositioned data modeling evaluated with quantum probability, neural field theories, filamentary signaling, and quantum nanoscience. Third is neuroscience physics interpretations of foundational physics findings in the context of neurobiology. The benefit of this work is the possibility of an improved understanding of the resolution of neuropathologies such as Alzheimer's disease. [ABSTRACT FROM AUTHOR]

This paper presents the theoretical states of radiation field in the mechanism of enzyme, for state of thermal and coherent radiation by concept of the quantum mechanics. For illustrating the energy and distribution of photon, we used simple concepts of the radiation field in the enzyme. We try to present the thermal radiation and coherent radiation happened in the biological microscopic system especially in the enzyme, and show that, these radiations could break the hydrogen bond pairs in the enzyme (substrate) at high temperature (above 323K) and show its effects on the relative activity of the enzyme.

We theoretically and computationally study the low-Reynolds-number hydrodynamics of a linear active microswimmer surfing on a compressible thin fluid layer characterized by an odd viscosity. Since the underlying three-dimensional fluid is assumed to be very thin compared to any lateral size of the fluid layer, the model is effectively two-dimensional. In the limit of small odd viscosity compared to the even viscosities of the fluid layer, we obtain analytical expressions for the self-induced flow field, which includes non-reciprocal components due to the odd viscosity. On this basis, we fully analyze the behavior of a single linear swimmer, finding that it follows a circular path, the radius of which is, to leading order, inversely proportional to the magnitude of the odd viscosity. In addition, we show that a pair of swimmers exhibits a wealth of two-body dynamics that depends on the initial relative orientation angles as well as on the propulsion mechanism adopted by each swimmer. In particular, the pusher–pusher and pusher–puller-type swimmer pairs exhibit a generic spiral motion, while the puller–puller pair is found to either co-rotate in the steady state along a circular trajectory or exhibit a more complex chaotic behavior resulting from the interplay between hydrodynamic and steric interactions. Our theoretical predictions may pave the way toward a better understanding of active transport in active chiral fluids with odd viscosity, and may find potential applications in the quantitative microrheological characterization of odd-viscous fluids.

Parrondo's paradox refers to the paradoxical phenomenon of combining two losing strategies in a certain manner to obtain a winning outcome. It has been applied to uncover unexpected outcomes across various disciplines, particularly at different spatiotemporal scales within ecosystems. In this article, we provide a comprehensive review of recent developments in Parrondo's paradox within the interdisciplinary realm of the physics of life, focusing on its significant applications across biology and the broader life sciences. Specifically, we examine its relevance from genetic pathways and phenotypic regulation, to intercellular interaction within multicellular organisms, and finally to the competition between populations and species in ecosystems. This phenomenon, spanning multiple biological domains and scales, enhances our understanding of the unified characteristics of life and reveals that adaptability in a drastically changing environment, rather than the inherent excellence of a trait, underpins survival in the process of evolution. We conclude by summarizing our findings and discussing future research directions that hold promise for advancing the field., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The cell cortex is a highly dynamic network of cytoskeletal filaments in which motor proteins induce active cortical stresses which in turn drive dynamic cellular processes such as cell motility, furrow formation or cytokinesis during cell division. Here, we develop a three-dimensional computational model of a cell cortex in the viscous limit including active cortical flows. Combining active gel and thin shell theory, we base our computational tool directly on the force balance equations for the velocity field on a discretized and arbitrarily deforming cortex. Since our method is based on the general force balance equations, it can easily be extended to more complex biological dependencies in terms of the constitutive laws or a dynamic coupling to a suspending fluid. We validate our algorithm by investigating the formation of a cleavage furrow on a biological cell immersed in a passive outer fluid, where we successfully compare our results to axi-symmetric simulations. We then apply our fully three-dimensional algorithm to fold formation and to study furrow formation under the influence of non-axisymmetric disturbances such as external shear. We report a reorientation mechanism by which the cell autonomously realigns its axis perpendicular to the furrow plane thus contributing to the robustness of cell division under realistic environmental conditions.

Human augmentation, human observer, biological physics, quantum physics, speed of light, information processing Based on a rough estimation, it had been estimated that velocity of neural integration in the cortical paths in the human brain may be close to the speed of light, i.e., to reach 2.28 ×10 SP 8 sp I ms i SP -1 sp that is ~0.76 of light speed (0.76 × I c i ) (Ghaderi, [13]). Keywords: human augmentation; human observer; biological physics; quantum physics; speed of light; information processing EN human augmentation human observer biological physics quantum physics speed of light information processing 1 4 4 06/23/21 20210617 NES 210617 Einstein special relativity theory (SRT) suggests that (i) no signal can cause an effect outside the source light cone, the space-time surface on which light rays emanate from the source, and (ii) no signal can move faster than light through a vacuum (Garrison et al., [12]). Theoretically, if by a given selective enhancement it becomes possible to increase the velocity of neural information transfer, i.e., to reach or exceed the speed of light; then some basic laws of physics including the limitations imposed by the speed of light may be violated. [Extracted from the article]

Abstract Background ESCRT-III is a membrane remodelling filament with the unique ability to cut membranes from the inside of the membrane neck. It is essential for the final stage of cell division, the formation of vesicles, the release of viruses, and membrane repair. Distinct from other cytoskeletal filaments, ESCRT-III filaments do not consume energy themselves, but work in conjunction with another ATP-consuming complex. Despite rapid progress in describing the cell biology of ESCRT-III, we lack an understanding of the physical mechanisms behind its force production and membrane remodelling. Results Here we present a minimal coarse-grained model that captures all the experimentally reported cases of ESCRT-III driven membrane sculpting, including the formation of downward and upward cones and tubules. This model suggests that a change in the geometry of membrane bound ESCRT-III filaments—from a flat spiral to a 3D helix—drives membrane deformation. We then show that such repetitive filament geometry transitions can induce the fission of cargo-containing vesicles. Conclusions Our model provides a general physical mechanism that explains the full range of ESCRT-III-dependent membrane remodelling and scission events observed in cells. This mechanism for filament force production is distinct from the mechanisms described for other cytoskeletal elements discovered so far. The mechanistic principles revealed here suggest new ways of manipulating ESCRT-III-driven processes in cells and could be used to guide the engineering of synthetic membrane-sculpting systems.

The article is devoted to the use of elements of historicism in classes of medical and biological physics. The possibility of raising the interest and motivation of students, developing ideas about the formation of science through the analysis of experiments and models is revealed. The use of elements of history shows that knowledge about the world around us, the laws of its existence, and the principles of its construction are continuously developing, deepening, and improving, so the formation of a modern specialist in any field of activity is impossible without the knowledge of the development of science and the tasks facing modern science. Turning to historical facts, one can, on the example of biographies of famous scholars, show that there were progressive thoughts on the use of scientific advances for the benefit of humanity. The use of historical material in classes on medical and biological physics contributes to the formation of students logical thinking, world outlook, memory development, patriotic education, active civic stance, students’ interest in the subject, and, as a result, increased motivation for learning, the formation of scientific world perception, the formation of the moral qualities of a future doctor, the creation of basis for the formation of an individual. Speaking about the life of well-known scholars, the teacher shows that their scientific and creative work shows that scientific research is a difficult and important work that embodies hopes, doubts, creative quest, disappointment, the aspiration of something new, the accomplishment of the goal, the dedication to its purpose. All of the above makes it possible to use historical facts to form students’ medical qualities and moral qualities that will be useful to them in future professional activities. By introducing students to the world of well-known scholars, the teacher contributes to the formation of an active life position of youth, the ability to set and achieve goals, to use their achievements for the benefit of humanity. Using historical material as to the development and emergence of a new directions in medicine – medical radiology, medical students cannot reproduce original research in the educational process, but they can trace the historical development and development of this research direction. This creates the effect of presence of students at the time and in the circumstances when the discovery was made, which helps to convince them of the authenticity of historical information. The use of historical information in classes contributes to the development of students’ thinking. Showing at the lessons the evolution of physics, the teacher reveals the role of practice as a source of knowledge and a criterion of truth and ensures deeper understanding of the laws of nature. Thus, the history of physics allows students to discover the general laws and principles of scientific knowledge. An example of a practical lesson on «Physical basis of nuclear medicine. (Determination of radioactive background, the activity of preparation, radioactivity, and dosimetry of ionizing radiation)» is given in the article.

We review a theoretical, coarse-grained description for cardiomyocytes calcium dynamics that is motivated by experiments on RyR channel dynamics and provides an analogy to other spontaneously oscillating systems. We show how a minimal model, that focuses on calcium channel and pump dynamics and kinetics, results in a single, easily understood equation for spontaneous calcium oscillations (the Van-der-Pol equation). We analyze experiments on isolated RyR channels to quantify how the channel dynamics depends both on the local calcium concentration, as well as its temporal behavior (“adaptation”). Our oscillator model analytically predicts the conditions for spontaneous oscillations, their frequency and amplitude, and how each of those scale with the small number of relevant parameters related to calcium channel and pump activity. The minimal model is easily extended to include the effects of noise and external pacing (electrical or mechanical). We show how our simple oscillator predicts and explains the experimental observations of synchronization, “bursting” and reduction of apparent noise in the beating dynamics of paced cells. Thus, our analogy and theoretical approach provides robust predictions for the beating dynamics, and their biochemical and mechanical modulation.

We formulate an active-gel theory for multicellular migration in the extra-cellular matrix (ECM). The cells are modeled as an active, polar solvent, and the ECM as a viscoelastic solid. Our theory enables to analyze the dynamic reciprocity between the migrating cells and their environment in terms of distinct relative forces and alignment mechanisms. We analyze the linear stability of polar cells migrating homogeneously in the ECM. Our theory predicts that, as a consequence of cell-matrix alignment, contractile cells migrate homogeneously for small wave vectors, while sufficiently extensile cells migrate in domains. Homogeneous cell migration of both extensile and contractile cells may be unstable for larger wave vectors, due to active forces and the alignment of cells with their concentration gradient. These mechanisms are stabilized by cellular alignment to the migration flow and matrix stiffness. They are expected to be suppressed entirely for rigid matrices with elastic moduli of order 10 kPa. Our theory should be useful in analyzing multicellular migration and ECM patterning at the mesoscopic scale.

We review a theoretical, coarse-grained description for cardiomyocytes calcium dynamics that is motivated by experiments on RyR channel dynamics and provides an analogy to other spontaneously oscillating systems. We show how a minimal model, that focuses on calcium channel and pump dynamics and kinetics, results in a single, easily understood equation for spontaneous calcium oscillations (the Van-der-Pol equation). We analyze experiments on isolated RyR channels to quantify how the channel dynamics depends both on the local calcium concentration, as well as its temporal behavior ("adaptation"). Our oscillator model analytically predicts the conditions for spontaneous oscillations, their frequency and amplitude, and how each of those scale with the small number of relevant parameters related to calcium channel and pump activity. The minimal model is easily extended to include the effects of noise and external pacing (electrical or mechanical). We show how our simple oscillator predicts and explains the experimental observations of synchronization, "bursting" and reduction of apparent noise in the beating dynamics of paced cells. Thus, our analogy and theoretical approach provides robust predictions for the beating dynamics, and their biochemical and mechanical modulation. [ABSTRACT FROM AUTHOR]

Filaments in the cell commonly treadmill. Driven by energy consumption, they grow on one end while shrinking on the other, causing filaments to appear motile even though individual proteins remain static. This process is characteristic of cytoskeletal filaments and leads to collective filament self-organization. Here we show that treadmilling drives filament nematic ordering by dissolving misaligned filaments. Taking the bacterial FtsZ protein involved in cell division as an example, we show that this mechanism aligns FtsZ filaments in vitro and drives the organization of the division ring in living Bacillus subtilis cells. We find that ordering via local dissolution also allows the system to quickly respond to chemical and geometrical biases in the cell, enabling us to quantitatively explain the ring formation dynamics in vivo. Beyond FtsZ and other cytoskeletal filaments, our study identifies a mechanism for self-organization via constant birth and death of energy-consuming filaments., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

The nuclear pore complex regulates nucleocytoplasmic transport by means of a tightly synchronized suite of biochemical reactions. The physicochemical properties of the translocating cargos are emerging as master regulators of their shuttling dynamics. As well as being affected by molecular weight and surface-exposed amino acids, the kinetics of the nuclear translocation of protein cargos also depend on their nanomechanical properties, yet the mechanisms underpinning the mechanoselectivity of the nuclear pore complex are unclear. Here we show that proteins with locally soft regions in the vicinity of the nuclear-localization sequence exhibit higher nuclear-import rates, and that such mechanoselectivity is specifically impaired upon knocking down nucleoporin 153, a key protein in the nuclear pore complex. This allows us to design a short, easy-to-express and chemically inert unstructured peptide tag that accelerates the nuclear-import rate of stiff protein cargos. We also show that U2OS osteosarcoma cells expressing the peptide-tagged myocardin-related transcription factor import this mechanosensitive protein to the nucleus at higher rates and display faster motility. Locally unstructured regions lower the free-energy barrier of protein translocation and might offer a control mechanism for nuclear mechanotransduction., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

Contraction and flow of the actin cell cortex have emerged as a common principle by which cells reorganize their cytoplasm and take shape. However, how these cortical flows interact with adjacent cytoplasmic components, changing their form and localization, and how this affects cytoplasmic organization and cell shape remains unclear. Here we show that in ascidian oocytes, the cooperative activities of cortical actomyosin flows and deformation of the adjacent mitochondria-rich myoplasm drive oocyte cytoplasmic reorganization and shape changes following fertilization. We show that vegetal-directed cortical actomyosin flows, established upon oocyte fertilization, lead to both the accumulation of cortical actin at the vegetal pole of the zygote and compression and local buckling of the adjacent elastic solid-like myoplasm layer due to friction forces generated at their interface. Once cortical flows have ceased, the multiple myoplasm buckles resolve into one larger buckle, which again drives the formation of the contraction pole-a protuberance of the zygote's vegetal pole where maternal mRNAs accumulate. Thus, our findings reveal a mechanism where cortical actomyosin network flows determine cytoplasmic reorganization and cell shape by deforming adjacent cytoplasmic components through friction forces., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)

During embryonic morphogenesis, tissues undergo dramatic deformations in order to form functional organs. Similarly, in adult animals, living cells and tissues are continually subjected to forces and deformations. Therefore, the success of embryonic development and the proper maintenance of physiological functions rely on the ability of cells to withstand mechanical stresses as well as their ability to flow in a collective manner. During these events, mechanical perturbations can originate from active processes at the single-cell level, competing with external stresses exerted by surrounding tissues and organs. However, the study of tissue mechanics has been somewhat limited to either the response to external forces or to intrinsic ones. In this work, we use an active vertex model of a 2D confluent tissue to study the interplay of external deformations that are applied globally to a tissue with internal active stresses that arise locally at the cellular level due to cell motility. We elucidate, in particular, the way in which this interplay between globally external and locally internal active driving determines the emergent mechanical properties of the tissue as a whole. For a tissue in the vicinity of a solid-fluid jamming or unjamming transition, we uncover a host of fascinating rheological phenomena, including yielding, shear thinning, continuous shear thickening, and discontinuous shear thickening. These model predictions provide a framework for understanding the recently observed nonlinear rheological behaviors in vivo .

The spiking activity of neocortical neurons exhibits a striking level of variability, even when these networks are driven by identical stimuli. The approximately Poisson firing of neurons has led to the hypothesis that these neural networks operate in the asynchronous state. In the asynchronous state, neurons fire independently from one another, so that the probability that a neuron experience synchronous synaptic inputs is exceedingly low. While the models of asynchronous neurons lead to observed spiking variability, it is not clear whether the asynchronous state can also account for the level of subthreshold membrane potential variability. We propose a new analytical framework to rigorously quantify the subthreshold variability of a single conductance-based neuron in response to synaptic inputs with prescribed degrees of synchrony. Technically, we leverage the theory of exchangeability to model input synchrony via jump-process-based synaptic drives; we then perform a moment analysis of the stationary response of a neuronal model with all-or-none conductances that neglects postspiking reset. As a result, we produce exact, interpretable closed forms for the first two stationary moments of the membrane voltage, with explicit dependence on the input synaptic numbers, strengths, and synchrony. For biophysically relevant parameters, we find that the asynchronous regime yields realistic subthreshold variability (voltage variance ≃4-9 mV 2 ) only when driven by a restricted number of large synapses, compatible with strong thalamic drive. By contrast, we find that achieving realistic subthreshold variability with dense cortico-cortical inputs requires including weak but nonzero input synchrony, consistent with measured pairwise spiking correlations. We also show that, without synchrony, the neural variability averages out to zero for all scaling limits with vanishing synaptic weights, independent of any balanced state hypothesis. This result challenges the theoretical basis for mean-field theories of the asynchronous state.

Many biological processes, including tissue morphogenesis, are driven by cell sorting. However, the primary mechanical drivers of sorting in multicellular aggregates (MCAs) remain controversial, in part because there is no appropriate computational model to probe mechanical interactions between cells. To address this important issue, we developed a three-dimensional, local forcebased simulation based on the subcellular element method. In our method, cells are modelled as collections of locally interacting force-bearing elements. We use the method to investigate the effects of tension and cell-cell adhesion on MCA sorting. We predict a minimum level of adhesion to produce insideout sorting of two cell types, which is in excellent agreement with observations in several developmental systems. We also predict the level of tension asymmetry needed for robust sorting. The generality and flexibility of the method make it applicable to tissue self-organization in a myriad of other biological processes, such as tumorigenesis and embryogenesis. [ABSTRACT FROM AUTHOR]

Clathrin-mediated endocytosis is one of the major pathways by which cells internalise cargo molecules. Recently it has been shown that clathrin triskelia can first assemble as flat lattices before the membrane starts to bend. However, for fully assembled clathrin lattices high energetic and topological barriers exist for the flat-to-curved transition. Here we explore the possibility that flat clathrin lattices grow with vacancies that are not visible in traditional imaging techniques but would lower these barriers. We identify the Eden model for cluster growth as the most appropriate modeling framework and systematically derive the four possible variants that result from the specific architecture of the clathrin triskelion. Our computer simulations show that the different models lead to clear differences in the statistical distributions of cluster shapes and densities. Experimental results from electron microscopy and correlative light microscopy provide first indications for the model variants with a moderate level of lattice vacancies.