Abstract
Cell and tissue nanomechanics, being inspired by progress in high-resolution physical mapping, has recently burst into biomedical research, discovering not only new characteristics of normal and diseased tissues, but also unveiling previously unknown mechanisms of pathological processes. Some parallels can be drawn between early development and carcinogenesis. Early embryogenesis, up to the blastocyst stage, requires a soft microenvironment and internal mechanical signals induced by the contractility of the cortical actomyosin cytoskeleton, stimulating quick cell divisions. During further development from the blastocyst implantation to placenta formation, decidua stiffness is increased ten-fold when compared to non-pregnant endometrium. Organogenesis is mediated by mechanosignaling inspired by intercellular junction formation with the involvement of mechanotransduction from the extracellular matrix (ECM). Carcinogenesis dramatically changes the mechanical properties of cells and their microenvironment, generally reproducing the structural properties and molecular organization of embryonic tissues, but with a higher stiffness of the ECM and higher cellular softness and fluidity. These changes are associated with the complete rearrangement of the entire tissue skeleton involving the ECM, cytoskeleton, and the nuclear scaffold, all integrated with each other in a joint network. The important changes occur in the cancer stem-cell niche responsible for tumor promotion and metastatic growth. We expect that the promising concept based on the natural selection of cancer cells fixing the most invasive phenotypes and genotypes by reciprocal regulation through ECM-mediated nanomechanical feedback loop can be exploited to create new therapeutic strategies for cancer treatment.
Highlights
Introduction published maps and institutional affilDifferent cells formed from the same or different germ layers communicate by complex biochemical and mechanical interactions
The mechanical forces that affect the formation of the fetus in the early stages of embryonic development include two main factors that affect the behavior of cells: the mechanical rigidity of the local tissue environment, including the cells and the extracellular matrix, and the contractile activity of the cells of the microenvironment
Due to the fact that cancer cells retain their ability to proliferate over a long period of time, and are exposed to immunity and negative factors associated with tumor growth, there is a steady generational change, and a form of “natural selection” for the most adapted clones [120]
Summary
The cytoskeleton is a key factor that defines the nanomechanical properties of the cell surface. Such a change in the geometry of the actin filaments may indicate a compensatory reaction of the cells to a mechanical stimulus; the stretching or compression of the cell membrane causes tension in the proteins of the cytoskeleton and can cause them to stretch, which downregulates the Hippo pathway and leads to the release of the YAP/TAZ complex from the nucleus [50] and the inhibition of cell proliferation Another class of cytoskeleton fibers microtubules has a significant role in cellular mechanics and the maintenance of cell structure. Cytoskeleton fibers play a major role in ultrastructural organization of the cellular cytoplasm and nucleoplasm, and form a specific structure that involves all four biological compounds: lipids, proteins, carbohydrates, and nucleic acids [55,56]
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