Reconstituting the nonequilibrium biophysics of the LECA cytoskeleton in active matter

Abstract

The eukaryotic cytoskeleton is a dense network of filaments and motor proteins that enables nearly all cellular force-generating behaviors, including movement, internal transport, and genome segregation through the mitotic spindle. Even though prokaryotes contain homologous force-generating filaments that drive processes like motion and cell division, no motor proteins have been found in bacterial and archaeal genomes. Current models suggest that eukaryotes emerged from the endosymbiosis and coevolution of two prokaryotic organisms; however, bioinformatic reconstructions reveal a LECA (Last Eukaryotic Common Ancestor) with multiple families of filaments and motor proteins. In this project, we aim to explore how the cytoskeleton underwent such a radical functional expansion during eukaryotic evolution, as well as to reconstruct a minimal active matter model of the LECA cytoskeleton. To do so, we built a computational-experimental platform to identify and synthesize cytoskeletal components in vitro and characterize their self-organizing properties with functional assays. As a proof of concept, we generated two synthetic protozoan motors, one of which produces a novel phase with ballistic microtubule motion. With this approach, our future work will expand our platform to a broader range of cytoskeletal components, including prokaryotic filaments. By exploring diverse eukaryotic and hybrid (eukaryote-prokaryote) cytoskeletal systems under multiple physiological conditions, we aim to provide insights into the evolution of eukaryotic active matter.

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