The biochemistry of cellular life occurs in solutions with ~ 130 – 150 mM of dissolved monovalent salts such as NaCl or KCl (salty solutions) compartmentalized within phospholipid bilayers. Single-walled giant vesicles with diameters &gt; 1 μm are minimal mimics of these compartments.  However, appreciable self-assembly of lipid films into giant vesicles occurs only in distilled or ultrapure water and fails in salty solutions.  These observations have posed long-standing technological challenges for assembling cell-mimetic compartments at scales suitable for applications in drug delivery, synthetic biology, and biophysics and raise questions about how and where primitive compartments arose at the origins of life.  Using quantitative characterization methods, we have made progress in understanding the mechanism of vesicle assembly in salty solutions and demonstrate a simple pathway for obtaining large quantities of cell-sized vesicles in solutions of physiological ionic strengths. In addition to providing a long-sought after goal of high yield assembly of giant vesicles in salty solutions, our results suggest previously unconsidered pathways for abiotic assembly of cell-sized vesicles from surfactant molecules in the extant and primitive earth.

Mechanistic insights enable high yield assembly of cell-mimetic giant vesicles in solutions of physiological ionic strengths

ACS Spring 2022

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