Publication date: 25th July 2016
There is a growing body of evidence showing that the physical and mechanical properties of the extracellular environment play a guiding, sometimes even deterministic role in cell behavior, for instance during development, wound healing, and cancer metastasis. Cells are able to sense physical and mechanical cues from the extracellular matrix (ECM) and transduce these cues into intracellular signals that can, in turn, affect cell response. While many studies have focused on identifying the molecular machineries underlying these mechanosensing and mechanotransduction processes, surprisingly little is known about what the cells are actually sensing, especially in the context of the typically complex, nonlinear, and fibrillar ECM.
To shed light on this question, we systematically modulated the microstructure and mechanical properties of ECM at the micro- and nano-scale and show that cell spreading, migration, and differentiation are determined by the properties of individual fibers within fibrous ECM, rather than by the bulk properties of the matrix. Importantly, the story does not end there, as cells were found to actively modify their local ECM properties, both physically and biochemically. Using spatially-resolved microrheological technique, we found that cells ‘prime’ their surrounding matrix, resulting in pockets of remodeled microenvironment that better support cell contractility. Furthermore, such local and dynamic modulation of ECM properties leads to spatiotemporally heterogeneous phenotype within cell populations, as cells continue to adapt to their immediate biophysical microenvironment. These results reveal the importance of looking at micro-scale cell–matrix interactions in understanding macro-scale cell and tissue response.
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