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In this review, we shed light on recent advances regarding the characterization of biochemical pathways of cellular mechanosensing and mechanotransduction with particular attention to their role in neurodegenerative disease pathogenesis. While the mechanistic components of these pathways are mostly uncovered today, the crosstalk between mechanical forces and soluble intracellular signaling is still not fully elucidated. Here, we recapitulate the general concepts of mechanobiology and the mechanisms that govern the mechanosensing and mechanotransduction processes, and we examine the crosstalk between mechanical stimuli and intracellular biochemical response, highlighting their effect on cellular organelles’ homeostasis and dysfunction. In particular, we discuss the current knowledge about the translation of mechanosignaling into biochemical signaling, focusing on those diseases that encompass metabolic accumulation of mutant proteins and have as primary characteristics the formation of pathological intracellular aggregates, such as Alzheimer’s Disease, Huntington’s Disease, Amyotrophic Lateral Sclerosis and Parkinson’s Disease. Overall, recent findings elucidate how mechanosensing and mechanotransduction pathways may be crucial to understand the pathogenic mechanisms underlying neurodegenerative diseases and emphasize the importance of these pathways for identifying potential therapeutic targets.

The biomedical translational applications of functionalized nanoparticles require comprehensive studies on their effect on human stem cells. Here, we have tested neat star-shaped mesoporous silica nanoparticles (s-MSN) and their chemically functionalized derivates; we examined nanoparticles (NPs) with similar dimensions but different surface chemistry, due to the amino groups grafted on silica nanoparticles (s-MSN-NH2), and gold nanoseeds chemically adsorbed on silica nanoparticles (s-MSN-Au). The different samples were dropped on glass coverslips to obtain a homogeneous deposition differing only for NPs’ chemical functionalization and suitable for long-term culture of human Bone Marrow–Mesenchymal stem cells (hBM-MSCs) and Adipose stem cells (hASCs). Our model allowed us to demonstrate that hBM-MSCs and hASCs have comparable growth curves, viability, and canonical Vinculin Focal adhesion spots on functionalized s-MSN-NH2 and s-MSN-Au as on neat s-MSN and control systems, but also to show morphological changes on all NP types compared to the control counterparts. The new shape was stem-cell-specific and was maintained on all types of NPs. Compared to the other NPs, s-MSN-Au exerted a small genotoxic effect on both stem cell types, which, however, did not affect the stem cell behavior, likely due to a peculiar stem cell metabolic restoration response.

Herein we present the production of novel nanocomposite films consisting of polylactic acid (PLA) polymer and the inclusion of nanoparticles of lignin (LNP), ZnO and hybrid ZnO@LNP (ZnO, 3.5% wt, ICP), characterized by similar regular shapes and different diameter distribution (30–70 nm and 100–150 nm, respectively). The obtained set of binary, ternary and quaternary systems were similar in surface wettability and morphology but different in the tensile performance: while the presence of LNP and ZnO in PLA caused a reduction of elastic modulus, stress and deformation at break, the inclusion of ZnO@LNP increased the stiffness and tensile strength (σb = 65.9 MPa and EYoung = 3030 MPa) with respect to neat PLA (σb = 37.4 MPa and EYoung = 2280 MPa). Neat and nanocomposite PLA-derived films were suitable for adult human bone marrow-mesenchymal stem cells and adipose stem cell cultures, as showed by their viability and behavior comparable to control conditions. Both stem cell types adhered to the films’ surface by vinculin focal adhesion spots and responded to the films’ mechanical properties by orchestrating the F-actin–filamin A interaction. Collectively, our results support the biomedical application of neat- and nanocomposite-PLA films and, based on the absence of toxicity in seeded stem cells, provide a proof of principle of their safety for food packaging purposes.