Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Poster Abstracts

22-POS Board 16 SIMULATIONS AND EXPERIMENTS REVEAL HOW A HETEROGENEOUS LIPID COMPOSITION IN MODEL PROTOCELL MEMBRANES MODULATES STABILITY AND PERMEABILITY Collin Nisler 1 ; 1 University of Chicago, Chemistry, Chicago, IL, USA The transformation from a non-living collection of interacting molecules to a self-replicating system capable of Darwinian evolution marks the origin of life on Earth. While a plethora of chemical and physical processes are necessary for the origin and evolution of complex life, encapsulation is widely recognized as a fundamental requirement for the concentration and sequestering of early self-replicating molecules. Due to the lack of complex molecules required to tightly regulate traffic in and out of cells as seen in modern biology, primitive cells would have had to rely on inherent membrane properties to modulate the selective permeation of feedstock and byproduct molecules, while retaining longer functional molecules and remaining stable in response to various external selection pressures. Here, we present a combination of experiments as well as coarse-grain and all-atom molecular simulations to characterize the permeability, stability, and structure of membranes and vesicles composed of different mixtures of prebiotically plausible lipids. We find that a mixture of short-chain and long-chain fatty acids significantly enhances the stability relative to membranes formed by either lipid alone. Simulations suggest a tradeoff between membrane thickness and dynamics tunes the stability and permeability of fatty-acid membranes in a manner that depends on the size of the permeant and, in the case of RNA, the sequence. Our results provide fundamental insight into the function of potentially prebiotic protocells and will guide future efforts to design a self-sustaining protocell system.

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