CAREER: Deciphering Interconnectivity between Cell Cytoskeleton Forces, Mechanics, and Machinery

About This Grant

This Faculty Early Career Development (CAREER) project seeks to understand the engineering rules that drive cytoskeletal coordination and sensing. Cells serve as nature's smart materials, capable of repairing, reorganizing, and sensing their surroundings. A crucial part of this cellular machinery is the cytoskeleton, which is a dynamic network of proteins that generates force and movement. However, how the parts of the cytoskeleton work together at the molecular level to accomplish larger tasks necessary for life is not understood. The knowledge gained in this project will contribute deeper insight to life’s fundamental mechanisms. It will also provide tools to support challenges in bioengineering, such as creating cells from the bottom up or developing smart materials inspired by biological systems. Outreach and educational programs that build from these research efforts include creating summer research opportunities for student parents and establishing “Teach Through Outreach”, an outreach-based learning program for engineering students. Both have the overarching goal of broadening participation and increasing STEM exposure to underprivileged students in Mississippi. The cytoskeleton exhibits emergent properties meaning that its ensemble behavior is not simply the sum of its parts. Myosin II is a cytoskeletal motor protein essential for basic cellular functions, and its motility and force generation behavior are significantly different at the single molecule level versus when part of a larger group. Yet, what tells the motor how to behave in different environments in not understood. By “sequencing” the actomyosin mechanome, or the interconnected system of forces, mechanics, and machinery, the aim of this research is to systematically identify which environmental factors lead to specific motor behaviors. This understanding will advance the field of biomechanics and mechanobiology by revealing how motor proteins work together, adapt to mechanical signals within the cell, and contribute to essential processes like cell movement and division. The research goals of the project are to (1) evaluate how myosin ensemble synergy is influenced by soluble mechanical modulators, (2) understand how the mechanosensitive environment within the cytoskeletal network affects myosin force generation, and (3) investigate how the stiffness of the environment changes force output of motor protein ensembles. These goals will be accomplished through engineering customizable cytoskeletal ensembles in vitro and investigating their behavior using optical tweezers, fluorescence imaging, and a quartz crystal microbalance with dissipation monitoring. This project has the potential to further scientific discovery through enabling construction of minimalistic cell models to understand cellular processes and phenotypes, adding to the toolbox for creating biomimetic smart materials, and elucidating mechanisms of diseases that rely on mechanical feedback. This project is jointly funded by Biomechanics and Mechanobiology (BMMB) Program in the Division of Civil, Mechanical, and Manufacturing Innovation (CMMI) and the Established Program to Stimulate Competitive Research (EPSCoR). 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.