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The biophysical cues in the extracellular environment are known to have a significant effect on the behaviour of cells. This knowledge has motivated bioengineers to develop tailored materials to mimic the extracellular matrix in order to further investigate fundamental signaling pathways that govern mechanotransduction as well as to produce biomaterials for tissue repair and regeneration. This focus issue brings together recent developments in mechanobiology with comments and research that highlight fundamental processes such as integrin-mediated cell adhesion in response to mechanical loads and also how biophysical cues can regulate stemness, matrix deposition and disease progression.
As the role of biophysical cues in regulating cell behaviour is increasingly understood, more evidence in the field of bioengineering indicates how such signals can affect cells and tissues.
Single-cell force spectroscopy reveals rapid, biphasic integrin activation and reinforcement of cell–matrix bonds during the initial steps of fibroblast adhesion.
The influence of matrix stiffness and degradation on neural progenitor cell stemness was investigated in a three-dimensional culture system, highlighting the role of remodelling in enhancing cell-to-cell interaction and ultimately maintaining neural stemness.
Blocking the growth of new blood vessels has been shown to alter fibrosis in livers in a disease stage-specific manner. In vitro models of fibrosis were developed to understand this process, highlighting the role of environmental mechanics.
Advances in biomaterials have enabled control over desired cell responses. Here, the authors highlight key analytical and bioprocessing techniques, outlining a framework for incorporating these tools into designing functionally optimal biomaterials.
Biomaterials engineered with specific bioactive ligands, tunable mechanical properties and complex architecture have emerged as powerful tools to probe cell sensing and response to physical properties of their material surroundings, and ultimately provide designer approaches to control cell function.
The mechanical properties of biomaterials affect cell growth through mechanotransduction signals. Here, hydrogels with fast stress relaxation were developed and showed increased cartilage matrix formation by cartilage cells compared to slow relaxation hydrogels.
The physical properties of biomaterials affect cell behaviour. Here, the authors investigate how stiffness and degradation of hydrogels affect signalling pathways that modulate the maintenance of stemness of neural progenitor cells.
Integrins play an important role in the adhesion of cells to their matrix. Here, the authors investigate how fibroblasts respond to mechanical loads, at the onset of cell adhesion to fibronectin, in distinct phases that are modulated by integrins.
Angiogenesis has been implicated in fibrotic diseases of the liver. Here, the authors developed microniches that mimic angiogenesis during different stages of liver fibrosis, and demonstrate the role of mechanotransduction in fibrogenesis.
Soft embryonic stem cells respond to small localized forces by increasing cell protrusion and spreading; in contrast, cells that are differentiated from them—which are ten times stiffer—do not spread. The deformation of the cell cytoskeleton is thus shown to be an important determinant of cellular response to force.
Conventional methods for the selection of tumorigenic cells from cancer cell lines rely on stem-cell markers. It is now shown that soft fibrin gels promote the growth of colonies of tumorigenic cells from single cancer cells from mouse or human cancer cell lines, and that as few as ten fibrin-cultured cells can lead to the formation of tumours in mice more efficiently than marker-selected cells.
Cells can sense and respond to their environment through mechanical forces. However, how the cell’s cytoskeleton transmits forces and how cytoskeletal proteins respond to forces is largely unknown. Now, a combination of mechanical perturbations and multiscale modelling offers insights into the molecular mechanisms behind the observed variations in the accumulation kinetics of the involved proteins in response to different types of deformation.