EAGER: Integrative Computational Model for Mechanosensing and Subcellular Remodeling

Michigan State University, East Lansing MI

Investigators

Abstract

1148298/ Baek This EAGER award funded by the Biotechnology, Biochemical and Biomass Engineering Program in the CBET Division of NSF will be used to develop a computational framework to model subcellular remodeling that will take into account the active cellular mechanosensing, turn over of cytoskeletal constituents, and kinetics of key molecules associated with cell-substrate and cell-cell interactions. This computational framework will enable researchers to explore the biological complexity associated with mechanosensing and how biophysical cues from the cellular enviroment modulate cellular processes and cell phenotype. Intellectual Merit. Previous researchers have investigated mechanosensitive cellular behavior by focusing on the effects of mechanical states (stress, strain, stiffness) which are independent of the cell. In contrast, in this work a more active mechanism will be examined by which the cell feels the physical environment, i.e., the cell actively applies traction and senses the response of the substrate. The computational model developed in this work will use a constrained mixture approach to account for the pre-stress and turnover of subcellular components and their interactions with key molecules in the cell-substrate and cell-cell interfaces. The computational model will also include substratum in the computational domain such that interactions between the cytoskeletal remodeling and the deformation of the substrate are taken into account. Broader Impact. If successful, the computational tool will enable researchers to integrate quantitative measurements from experiments into the computational model to elucidate the cellular processes modulated by various mechanical and soluble cues. This study will also impact the tissue engineering and clinical communities by providing a predictive model that can be used in the design of engineered tissues and development of pharmaceutical treatment of diseases. From an educational standpoint, the project will provide a broad exposure to the students with an opportunity to integrate knowledge bases from vastly different fields. The PI has supported both (female and minority) undergraduate students and high school teachers from an existing NSF RET site program. The PI has been and will be actively engaged in K-12 education, RET, and public outreach programs such as Grandparents University. The outcomes of the research will be incorporated into these activities and the computational biomechanics course that the PI will be developing. The computational model and outcomes of this proposal will be disseminated through the web, in addition to traditional modes, such as journal publications and presentations at scientific meetings.