Many studies over the past decade have demonstrated that cells respond to the stiffness of the surrounding tissue by pulling on it and sensing the stiffness, a process known as mechanotransduction. Cells use these mechanotransduction signals to make a host of decisions regarding survival, migration, and differentiation into different cell types. Increased tissue stiffness often accompanies various diseases including fibrotic diseases and cancer. Previous studies suggest that these diseases may be driven by altered stiffness. However, there is another mechanical aspect of tissues that has not been studied to the same degree. Tissues in the human body are “viscoelasticâ€, meaning that they behave like both a thick liquid and a stretchable spring. While many studies have investigated how changing the stiffness of the “spring†component affects cells, there have been far fewer studies of the effects of the viscous “thickness†component of the tissue. In this research, the use of novel polymers to separately change the viscosity and the stiffness of the surface under cells and determine the cellular responses to each component will be explored. This work will improve our understanding of how cells respond to their surroundings, which could lead to significant advances in our understanding of human health.
Studies from the past two decades have convincingly convincingly that cells are able to sense the mechanical properties of their surroundings and make major decisions in response to this mechanosensation, including decisions regarding cell migration, proliferation, survival, and differentiation. The vast majority of these studies have focused on the cellular mechanoresponse to changing substrate stiffness (or elastic modulus) and have been conducted on purely elastic substrates. In contrast, most soft tissues in the human body exhibit viscoelastic behavior; that is, they generate responsive force proportional to both the magnitude and rate of strain. What role does the viscous component of viscoelastic tissue play in driving the cellular mechanoresponse? To answer this question, pairs of polymer substrates that have similar storage moduli (elastic component) but significantly different loss moduli (viscous component) are investigated. The storage moduli for these pairs spans the range of healthy to diseased soft tissue. The hypothesis is that increasing loss modulus produces similar effects to increasing storage modulus; in other words, cells on an increasingly viscous substrate respond as if they are on a stiffer substrate. Cell morphology, traction force generation, proliferation, migration, and differentiation to isolate the effects of viscous and elastic components of the substrate on cellular responses will be quantified. Based on that step, an existing computational model of cell-substrate mechanical interactions will be modified to develop a potential mechanism to explain this response mechanistically.
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