In this project the PIs will develop, validate and implement a computational-theoretical-experimental framework, referred to as Cellular Particle Dynamics (CPD), to quantitatively relate biomechanical properties at the cell level to those at the multicellular and tissue level. Within this formalism a cell, considered as a continuum material object with defined volume and adaptive shape, is coarse-grained into a finite number of equal volume elements. Each such element is represented by a point-like Cellular Particle (CP) situated at the center of the volume element. Interactions between the CPs determine their effective size (same as the size of the volume element they represent), as well as their dynamical behavior. Cell and multicellular level biomechanical properties (e.g. viscosities, elastic moduli) will be determined through the combined use of experiments and the proposed theory of continuum elastic and viscous media. The same biomechanical properties will also be measured computationally using the CPD framework, and results expressed in terms of parameters characterizing CPs and their interactions, the CPD parameters. Comparison of experiments and simulations will quantitatively relate CPD parameters to the biomechanical properties of both cells and multicellular assemblies. Once the CPD parameters have experimentally been calibrated, the formalism will provide a systematic framework to predict the time evolution of complex multicellular systems during shape-changing biomechanical transformations. As an application, the PIs will use the novel framework to guide ongoing efforts to fabricate tubular, lumen-containing functional organ structures (contractile vascular grafts). At present no systematic framework exists to analyze biomechanical processes that involve multiple scales, resulting from the combination of individual cell behavior and collective cell rearrangements and this project will fill this gap. Beyond this intellectual challenge that the proposal will address the project will contribute to the urgent practical societal need of fabricating functional replacement tissue and organ modules. The graduate students involved in these activities will be exposed to multiple scientific disciplines.
