Abstract
Mechanomics represents the natural progression of knowledge at the intersection of mechanics and biology with the aim to codify the role of mechanical environment on biological adaptation. Compared to the mapping of the human genome, the challenge of mapping the mechanome remains unsolved. Solving this grand challenge will require both top down and bottom up R&D approaches using experimental and computational tools to visualize and measure adaptation as it occurs. Akin to a mechanical test of a smart material that changes its mechanical properties and local environment under load, stem cells adapt their shape, cytoskeletal architecture, intrinsic mechanical properties, as well as their own niche, through cytoskeletal adaptation as well as up- and down-regulation of structural proteins that modulate their mechanical milieux. Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, reconfiguring of cytoskeletal machinery (nucleus, cytoskeleton), in response to controlled mechanical forces and stresses applied at cellular boundaries. Coupled with multiphysics computational and virtual power theoretical approaches, these novel experimental approaches enable mechanical testing of stem cells, multicellular templates, and tissues inhabited by stem cells, while the stem cells themselves evolve over time. The novel approach is paving the way to decipher mechanisms of structural and functional adaptation of stem cells in response to controlled mechanical cues. This mini-review outlines integrated approaches and methodologies implemented to date in a series of studies carried out by our consortium. The consortium’s body of work is described in context of current roadblocks in the field and innovative, breakthrough solutions and is designed to encourage discourse and cross disciplinary collaboration in the scientific community.
Highlights
Mechanomics studies the influence of forces on biological structure and function, across length scales, from molecules to cells, to tissues, to organs and organ systems that make up organisms
Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, their cytoskeletal machinery and local environment, in response to controlled mechanical forces and stresses applied at cellular boundaries
This, together with measurements of changes in baseline gene transcription of factors indicative of lineage commitment provided thousands of single cell data points that could be depicted as 95% confidence intervals, relating stress and strain to lineage commitment (Figure 1D), forming the basis of the first mechanome map of model embryonic murine mesenchymal stem cells (Song et al, 2013)
Summary
Mechanomics studies the influence of forces on biological structure and function, across length scales, from molecules to cells, to tissues, to organs and organ systems that make up organisms. Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, their cytoskeletal machinery (nucleus, cytoskeleton) and local environment, in response to controlled mechanical forces and stresses applied at cellular boundaries.
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