The Mechanobiology of 2D and 3D Multicellular Systems

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In the body, mammalian cells exist in a dynamic, three-dimensional microenvironment where numerous physical and biochemical cues interact to govern critical biological processes (e.g, stem cell fate, motility, mitosis, morphogenesis, etc.). Physical cues can include dynamic and time-dependent variations in local mechanical properties of the extra-cellular matrix (ECM), complex stresses and strains occurring in response to tissue stretching and compression during movement, or even changes in microenvironment shape and topography as a result of ECM remodelling and tissue movements. While cellular responses to biochemical molecules and gradients are well studied, the ability of cells to sense, integrate and respond to diverse and physical cues is not as well understood. To continue developing our understanding of mechanobiology, novel experimental protocols and devices are required to mimic the complexity of the cellular microenvironment. Such tools and related experimental approaches enable researchers to systematically expose cells to physical stimuli, measure their responses and uncover new knowledge. This leads to a deeper understanding of the critical role physical cues play in governing fundamental aspects of cell biology. We have been addressing these issues by engineering novel cell culture devices and approaches for exposing mammalian cells to systematically controlled physical stimuli. Utilizing these platforms, we have established experimental protocols to characterize some of the earliest structural responses of cells to changes in mechanical properties, microtopography and stress/strain occurring in the microenvironment. This has allowed elucidate how cells detect, integrate and respond to diverse physical stimuli and enhance our understanding of mechanobiology. These insights are allowing us to understand how complex physical stimuli are hard wired into underlying mechanobiological networks. These pathways have been shown to regulate normal healthy physiological processes and also appear to become disrupted in several disease pathologies. Importantly, our fundamental research has also been translated through commercialization, industry partnerships and licensed intellectual property. Our discoveries are driving innovation through the creation of new biomedical devices and technologies, as well as applications in bioengineering, cell bioprocessing, tissue engineering and regenerative medicine.