APS Logo

Polyelectrolyte coacervates as model protocells for stable RNA compartmentalization

ORAL

Abstract

One of the most intriguing questions in science is what the first cells, or protocells, containing genetic material looked like. Membraneless coacervate microdroplets have long been proposed as model protocells because they can grow, divide, and concentrate RNA through natural partitioning. The absence of a membrane, such as a lipid bilayer, allows coacervate protocells to easily recruit materials, such as building blocks for their genome, from the surroundings. However, lacking a membrane also presents two significant drawbacks. First, the protocells rapidly fuse together. Second, the genetic material continuously leaks out and exchanges with neighboring protocells. In my talk, I will describe a prebiotically plausible mechanism to stabilize the interface of coacervate droplets that simultaneously prevents their fusion and substantially reduces RNA exchange. We have found that transferring coacervates from their equilibrium supernatant to deionized water induces the formation of electrostatic crosslinks on their interfaces.1 These electrostatic crosslinks are driven by an osmotic expulsion of counterions from the interface of the droplets into bulk, ion-free water.2 Recently, we have uncovered the complex morphologies of coacervate protocells based on this stabilization that mimics cellular growth and death, in repeated cycles, for days. We propose that freshwater from rain, snow melt, etc., which usually have only trace amounts of salt ions, would have mimicked deionized water in creating viable coacervate protocells at the origins of life.3 I will also discuss our current efforts in non-enzymatic RNA replication and ribozyme catalysis in these coacervate protocells.

Publication: 1. A. Agrawal, J. F. Douglas, M. V. Tirrell, A. Karim, Manipulation of coacervate droplets with an electric field. Proc. Natl. Acad. Sci. U.S.A. 119, e2203483119 (2022).<br>2. A. Baksi, H. Zerze, A. Agrawal, A. Karim, G. H. Zerze, The molecular picture of the local environment in a stable model coacervate, Communications Chemistry, 7, 1 (2024).<br>3. A. Agrawal, A. Radakovic, A. Vonteddu, S. Rizvi, V. H. Huynh, J. F. Douglas, M. V. Tirrell, A. Karim, J. W. Szostak, Did the exposure of coacervate droplets to rain make them the first stable protocells?, Science Advances 10, eadn9657 (2024).

Presenters

  • Aman Agrawal

    University Of Chicago

Authors

  • Aman Agrawal

    University Of Chicago

  • Alamgir Karim

    University Of Houston, University of Houston

  • Matthew V Tirrell

    University of Chicago

  • Jack W Szostak

    University of Chicago