The fundamental questions that the PI aims to address in this CAREER project are: What are the principles underlying the formation of spatio-temporal patterns of Rho GTPases, and what is their functional role in regulating the mechanics of the cell cortex and cell deformation? What is the feedback between cell shape changes and cytoplasmic flow induced by mechanical (dynamic) deformation of the cell cortex and the chemical pattern of Rho GTPases? To address these questions, the PI will combine experiment and theory to identify the fundamental principles underlying this interplay between chemical patterns and mechanical cell deformations and thereby to lay the foundation for a comprehensive understanding of the dynamics of mechano-chemical patterns in animal cells. Uncovering the principles of mechano-chemical structure formation in biological systems will also facilitate new smart materials and soft robotics technology. The proposed research activities will be closely integrated with teaching activities at the interface of physics and biology. (i) The PI will continue to mentor high school students through the Research Science Institute at MIT. (ii) As a faculty mentor for the MIT Summer Research Program (MSRP) General, the PI will continue to mentor and to attract underrepresented students (minorities, women in STEM, or students with low socioeconomic status) to MIT to gain significant research experience and explore the possibility of doctoral education at MIT.
This project will combine novel experimental techniques, theory and mathematical modeling to elucidate how active mechanics and cell geometry, when coupled to chemical reactions, give rise to robust mechano-chemical patterns. Important life processes common to all animal cells such as cytokinesis and cellular migration require the interplay and coordination between chemical protein patterns and mechanical deformation of the cell shape. At the heart of both are active processes, driven and regulated by the highly conserved Rho family of GTPases and the action of myosin motors consuming ATP. Over the course of this project, the PI will construct, implement and experimentally validate a comprehensive theoretical model to quantify and to understand the mechanisms of mechano-chemical coupling between chemical patterns of Rho GTPases, mechanical cell deformations, and cytoplasmic flow. Starfish oocytes will be used as a biological model system to study mechano-chemical patterns during development in vivo, as they are a well-established system with a high degree of experimental accessibility. A novel imaging platform based on near-IR fluorescent single-walled carbon nanotubes will be developed to generate high resolution maps of cortex dynamics and mechanics during development. It will be combined with in vivo imaging of signaling protein localization, as well as biochemical, biophysical and optogenetic manipulations. As Rho GTPases are ubiquitous and in particular associated to the dynamic spatial structuring of cells, the investigations should reveal universal principles for the interplay of mechanical deformations and biochemical pattern formation.
This project is being jointly supported by the Physics of Living Systems program in the Division of Physics and the Cellular Dynammics and Function Cluster in the Division of Molecular and Cellular Biosciences.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
