BRITE Fellow: Systems-level Mechanobiology from the Cellular Mechanome to Sustainable Meat Production

University Of California-Los Angeles, Los Angeles CA

Investigators

Abstract

This Boosting Research Ideas for Transformative and Equitable Advances in Engineering (BRITE) Fellow grant will advance knowledge of cells as materials and translate findings for sustainable protein production. Biology is commonly described in terms of genomes and biochemical reactions. But the physical properties of cells are critical for many of the body’s functions. How cells deform to circulate through the body; how cells resist physical forces—like stretching or squeezing, and mechanical cues—like the stiffness of the cellular environment, are important for human health, and critical in many diseases. This project strives to understand the cellular ‘mechanome’, or the set of genes, proteins, and pathways that regulate how cells sense and respond to physical and mechanical cues. Findings would enable us to address fundamental questions including: How do cells integrate mechanical and soluble cues to regulate their behaviors? The vision of the research is to establish new foundational knowledge of cells as materials, and to translate this knowledge to develop innovative engineering methods to “grow” animal protein for foods. The research also includes initiatives to promote diversity in engineering and science research using food as a tool to strengthen mentorship and community. The specific goals of the research are to (1) build a systems-level knowledge of how cells sense and respond to mechanical stimuli and regulate their mechanical properties; and (2) test the hypothesis that the mechanical crosstalk between cells and scaffolds is critical for the sensory and nutrient properties of cultured meat. To build a unified knowledge of the mechanome, we will (i) investigate predicted mechanical regulators that emerged from our high throughput deformability screen; (ii) engineer a genome-wide screen to identify novel regulators of mechanical memory; and (iii) compile a mechanome web resource. To translate findings for food production, we aim to achieve efficient muscle tissue growth by (i) defining the optimal stiffness of edible microcarrier scaffolds for the myogenesis of livestock animal cells; and (ii) identifying combinations of scaffold stiffness and media additives to enhance satellite muscle cell proliferation and myotube contractility in a bioreactor context. Findings will enable the PI to address fundamental questions in mechanobiology with translational applications for protein production and tissue engineering. Complementary methods for protein production are urgently needed to address the increasing need to feed the world’s growing population to protect against disruptions in the food chain resulting from natural disasters or epidemics that limit or halt production. 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.