Physical Models for the Early Evolution of Cell Membranes

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Physical Models for the Early Evolution of Cell Membranes

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dc.contributor.advisor Szostak, Jack William
dc.contributor.author Budin, Itay
dc.date.accessioned 2012-11-14T13:59:17Z
dash.embargo.terms 2013-04-03 en_US
dash.embargo.terms 2013-04-03
dc.date.issued 2012-11-14
dc.date.submitted 2012
dc.identifier.other http://dissertations.umi.com/gsas.harvard:10565 en
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9904006
dc.description.abstract Cells use lipid membranes to organize and define their chemical environments. All cell membranes are based on a common structure: bilayers composed of phospholipids with two hydrocarbon chains. How did biology converge on this particular solution for cellular encapsulation? The first cell membranes are proposed to have assembled from simple, single-chain lipids, such as fatty acids and their derivatives, which would have been available in the prebiotic environment. Here we argue that the physical properties of fatty acid membranes would have made them well suited for a role as primitive cell membranes and predisposed their evolution to modern, phospholipid-based membranes. We first considered models for primitive membrane self-assembly, which faces significant concentration barriers due to the entropic cost of aggregation and the solubility of single-chain lipids. We therefore identified two physical mechanisms by which fatty acid membrane assembly can proceed from dilute solutions. Thermal diffusion columns, a proposed prebiotic concentration method, drive the formation of fatty acid vesicles by concentrating an initially isotropic solution past the critical concentration necessary for aggregation. Alternatively, mixtures of fatty acids with varying chain lengths, the expected products of abiotic lipid synthesis, intrinsically reduce the concentration barrier to aggregation through their polydispersity. These results motivated us to better understand the phase behavior of fatty acids in solutions. We found that the composition of fatty acid aggregates, whether vesicles or micelles, is also determined by concentration. Fatty acid vesicles feature significant amounts of coexisting micelles, whose abundance is enriched in low concentration solutions. We utilized this micelle-vesicle equilibrium to drive the growth of pre-existing fatty acid vesicles by changing amphiphile concentration. We next considered the evolution of phospholipid membranes, which was a critical and necessary step for the early evolution of cells. We found that the incorporation of even small amounts of phospholipids drives the growth of fatty acid vesicles by competition for monomers with neighboring vesicles lacking phospholipids. This competitive growth would have provided a strong selective advantage for primitive cells to evolve the catalytic machinery needed to synthesize phospholipids from their single-chain precursors. Growth is caused by any relative difference in phospholipid content, suggesting an evolutionary arms race among primitive cells for increasingly phospholipid membranes. What would have been the consequences for early cells of such a transition in membrane composition? We found that increasing phospholipid content inhibits the permeability of fatty acid membranes through changes in bilayer fluidity. For early heterotrophic cells, the emergence of increasingly phospholipid membranes would have therefore imposed new selective pressures for the evolution of membrane transport machinery and metabolism. Our model for early membrane evolution led us to develop prebiotic models for phospholipid chemistry. The assembly of phospholipids from single-chain substrates requires a single reaction: the acyltransfer of an activated fatty acid onto a glycerol monoester or lysophospholipid. We developed a synthetic model for this reaction that incorporates a copper-catalyzed azide-alkyne cycloaddition and showed that it drives de novo vesicle assembly. en_US
dc.language.iso en_US en_US
dash.license LAA
dc.subject biophysics en_US
dc.subject biochemistry en_US
dc.subject early evolution en_US
dc.subject fatty acids en_US
dc.subject membranes en_US
dc.subject origin of life en_US
dc.subject phospholipids en_US
dc.subject protocell en_US
dc.title Physical Models for the Early Evolution of Cell Membranes en_US
dc.type Thesis or Dissertation en_US
dc.date.available 2013-04-03T07:30:41Z
thesis.degree.date 2012 en_US
thesis.degree.discipline Biochemistry en_US
thesis.degree.grantor Harvard University en_US
thesis.degree.level doctoral en_US
thesis.degree.name Ph.D. en_US
dc.contributor.committeeMember Berg, Howard en_US
dc.contributor.committeeMember Guidotti, Guido en_US
dc.contributor.committeeMember Miller, Chris en_US

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