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Local mechanical properties are important to cellular function; but conventional measurement techniques are limited in intact, living, 3D tissues. Here, the authors report on swellable hydrogel microparticles to monitor mechanical properties in situ via a temperature change.

Cell-generated forces play a foundational role in tissue dynamics and homeostasis and are critically important in several biological processes, including cell migration, wound healing, morphogenesis, and cancer metastasis. Quantifying such forces in vivo is technically challenging and requires novel strategies that capture mechanical information across molecular, cellular, and tissue length scales, while allowing these studies to be performed in physiologically realistic biological models. Advanced biomaterials can be designed to non-destructively measure these stresses in vitro, and here, we review mechanical characterizations and force-sensing biomaterial-based technologies to provide insight into the mechanical nature of tissue processes. We specifically and uniquely focus on the use of these techniques to identify characteristics of cell and tissue “tensegrity:” the hierarchical and modular interplay between tension and compression that provide biological tissues with remarkable mechanical properties and behaviors. Based on these observed patterns, we highlight and discuss the emerging role of tensegrity at multiple length scales in tissue dynamics from homeostasis, to morphogenesis, to pathological dysfunction.

Understanding how forces orchestrate tissue formation requires technologies to map internal tissue stress at cellular length scales. Here, authors develop ultrasoft sensors that visibly deform under cell-generated stress to capture patterns of internal stress development during multicellular spheroid formation.

Summary: Integrin receptors coordinate cell adhesion to the extracellular matrix (ECM) to facilitate many cellular processes during malignant transformation. Despite their pro-tumorigenic roles, therapies targeting integrins remain limited. Here, we provide genetic evidence supporting a functional redundancy between β1 and β3 integrin during breast cancer progression. Although ablation of β1 or β3 integrin alone has limited effects on ErbB2-driven mammary tumorigenesis, deletion of both receptors resulted in a significant delay in tumor onset with a corresponding impairment in lung metastasis. Mechanistically, stiff ECM cooperates with integrin receptors to recruit insulin receptors (IRs) to focal adhesion through the formation of integrin/IR complexes, thereby preventing their lysosomal degradation. β1/β3 integrin-deficient tumors that eventually emerged exhibit impaired Akt/mTORC1 activity. Murine and human breast cancers exhibiting enhanced integrin-dependent activity also display elevated IR/Akt/mTORC1 signaling activity. Together, these observations argue that integrin/IR crosstalk transduces mechanical cues from the tumor microenvironment to promote ErbB2-dependent breast cancer progression. : Using a mouse model of ErbB2-driven breast cancer, Bui et al. demonstrate a functional redundancy between two integrin subunits, β1 and β3, during mammary tumorigenesis. Mechanistically, both extracellular matrix (ECM) and integrin receptors regulate insulin receptor (IR) activity to promote the Akt/mTORC1 signaling axis, a crucial pathway to malignant transformation. Keywords: ECM stiffness, ErbB2, breast cancer, insulin receptor, integrin, transgenic model, Akt, mTORC1