Probing spatiotemporal mechanobiology through novel dynamic material platforms - PROJECT SUMMARY The long-term goal of the Corbin lab is to study emergent time-dependent cellular responses through reimagining engineered microdevices. Cells engage in a continuous and dynamic interplay with their surroundings, and respond rapidly and with remarkable precision to variations in their mechanical environment including topography, stiffness, and stretching. There is a critical need to make an in-vitro system that sufficiently reflects the essential adaptive and maladaptive processes and phenotypic benchmarks to understand the vital link between biomechanics and cell structure and function. Materials with the ability to change mechanical properties have the potential to reshape our understanding of how cells interact with their micro-environments. Broadly, we seek to address two major challenges of dynamic engineering materials for mechanobiology interrogation: 1) tailoring effective and spatio-temporal realistic biomechanical cues to drive desirable interactions and responses and 2) manipulating and modeling the complex network of many signals operating on various lengths and timescales that determine cell fate. The Corbin lab has focused on developing a unifying engineered materials platform to deconstruct and decode how biological behavior can arise from a wide range of dynamic biomechanical stimuli. Major advances to date have included: (1) the evaluation of magnetorheological elastomers as a novel tunable and reversible biomechanics tool to study cardiomyocyte mechanosensitivity, (2) the discovery of pathologic mechanical increment induces rapid remodeling of cardiomyocytes, (3) the creation of local spatial mechanics and topographic mechanics with the same platform, and (4) quantify the directionality and magnitude of how spatial mechanics and chemical applications interfere or synergize with each other in time – in other terms how they “compete” or “cooperate.” In this proposal, we will dramatically enhance our efforts to engineer the elements of biological interaction with the dynamic mechanical microenvironment. We will expand our platform to include simultaneous control of stiffness gradients and adhesion gradients, local stimulation of substrate stiffness to examine the spread of mechanotransductive signaling, and cyclic variations in stiffness to mimic periodic biomechanical events. These future efforts are well suited to the research program, given the widely applicable framework to address the broader definition of invisible forces that intrinsically link cells and biomechanics.
