Permeation of membranes by the neutral form of amino acids and peptides: Relevance to the origin of peptide translocation

Abstract

The flux of amino acids and other nutrient solutes such as phosphate across lipid bilayers (liposomes) is 10(5) slower than facilitated inward transport across biological membranes. This suggest that primitive cells lacking highly evolved transport systems would have difficulty transporting sufficient nutrients for cell growth to occur. There are two possible ways by which early life may have overcome this difficulty: (1) The membranes of the earliest cellular life-forms may have been intrinsically more permeable to solutes; or (2) some transport mechanism may have been available to facilitate transbilayer movement of solutes essential for cell survival and growth prior to the evolution of membrane transport proteins. Translocation of neutral species represents one such mechanism. The neutral forms of amino acids modified by methylation (creating protonated weak bases) permeate membranes up to 10(10) times faster than charged forms. This increased permeability when coupled to a transmembrane pH gradient can result in significantly increased rates of net unidirectional transport. Such pH gradients can be generated in vesicles used to model protocells that preceded and were presumably ancestral to early forms of life. This transport mechanism may still play a role in some protein translocation processes (e.g. for certain signal sequences, toxins and thylakoid proteins) in vivo.

Permeation of the three aromatic dipeptides through lipid bilayers: Experimental and computational study

“…82,83 However, quantitatively the results are different. The permeation coefficient estimated for the neutral forms of NATA from Deamer's experiments is close to the permeation coefficient of water (P = 10 −2 cm s −1 ) while our permeation coefficient is considerably slower (P ∼ 10 −7 cm s −1 ).…”

110 Years of the Meyer–Overton Rule: Predicting Membrane Permeability of Gases and Other Small Compounds

“…In light of this, recent reports excluding endocytosis as an uptake mechanism do not appear convincing. [79] Since passive membrane diffusion of peptides has long been known as impossible, [80,81] what else can possibly be offered as a transport mechanism? Transient water wires across a lipid bilayer.…”

How did cells get their size?

“…As chain lengths of liposome-forming amphiphiles increases from 14 to 18 carbons (Paula et al, 1996) the availability of transient membrane defects serving as solute diffusion pathways declines markedly, producing a ϳ1,000-fold drop in ion permeability. Prebiotic liposomes with, e.g., eight to 10 carbon lipids, may have acquired solutes by unfacilitated fluxes (see also Chakrabarti and Deamer, 1994;Monnard and Deamer, 2001). Slow environmental dilutions were perhaps tolerated, but, before osmotic valves evolved, abrupt dilution would surely have caused lysis-especially in fragile thin-bilayer liposomes.…”