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1.
Cell ; 156(3): 428-39, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24462247

RESUMO

Although massive membrane rearrangements occur during cell division, little is known about specific roles that lipids might play in this process. We report that the lipidome changes with the cell cycle. LC-MS-based lipid profiling shows that 11 lipids with specific chemical structures accumulate in dividing cells. Using AFM, we demonstrate differences in the mechanical properties of live dividing cells and their isolated lipids relative to nondividing cells. In parallel, systematic RNAi knockdown of lipid biosynthetic enzymes identified enzymes required for division, which highly correlated with lipids accumulated in dividing cells. We show that cells specifically regulate the localization of lipids to midbodies, membrane-based structures where cleavage occurs. We conclude that cells actively regulate and modulate their lipid composition and localization during division, with both signaling and structural roles likely. This work has broader implications for the active and sustained participation of lipids in basic biology.


Assuntos
Divisão Celular , Membrana Celular/química , Lipídeos de Membrana/análise , Cromatografia Líquida , Citocinese , Diacilglicerol O-Aciltransferase/genética , Diacilglicerol O-Aciltransferase/metabolismo , Galactosilceramidase/genética , Galactosilceramidase/metabolismo , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Lipídeos de Membrana/biossíntese , Redes e Vias Metabólicas , Esfingomielina Fosfodiesterase/genética , Esfingomielina Fosfodiesterase/metabolismo
2.
Small ; 13(24)2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28503797

RESUMO

The nanomechanics of lipid membranes regulates a large number of cellular functions. However, the molecular mechanisms underlying the plastic rupture of individual bilayers remain elusive. This study uses force clamp spectroscopy to capture the force-dependent dynamics of membrane failure on a model diphytanoylphosphatidylcholine multilayer stack, which is devoid of surface effects. The obtained kinetic measurements demonstrate that the rupture of an individual lipid bilayer, occurring in the bilayer parallel plane, is a stochastic process that follows a log-normal distribution, compatible with a pore formation mechanism. Furthermore, the vertical individual force-clamp trajectories, occurring in the bilayer orthogonal bilayer plane, reveal that rupturing process occurs through distinct intermediate mechanical transition states that can be ascribed to the fine chemical composition of the hydrated phospholipid moiety. Altogether, these results provide a first description of unanticipated complexity in the energy landscape governing the mechanically induced bilayer rupture process.

3.
Phys Rev Lett ; 114(25): 258303, 2015 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-26197150

RESUMO

Confined liquids organize in solidlike layers at the liquid-substrate interface. Here we use force-clamp spectroscopy AFM to capture the equilibrium dynamics between the broken and reformed states of an individual solvation layer in real time. Kinetic measurements demonstrate that the rupture of each individual solvation layer in structured liquids is driven by the rupture of a single interaction for 1-undecanol and by two interactions in the case of the ionic liquid ethylammonium nitrate. Our results provide a first description of the energy landscape governing the molecular motions that drive the packing and self-assembly of each individual liquid layer.


Assuntos
Líquidos Iônicos/química , Modelos Químicos , Cinética , Microscopia de Força Atômica/métodos , Compostos de Amônio Quaternário/química , Soluções
4.
Curr Opin Chem Biol ; 29: 87-93, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26517566

RESUMO

The cell membrane is a highly complex designed material with remarkable physicochemical properties; comprised mainly of lipid moieties, it is capable of self-assembling, changing morphology, housing a range of distinct proteins, and withstanding electrical, chemical and mechanical perturbations. All of these fundamental cellular functions occurring within a 5nm thick film is an astonishing feat of engineering, made possible due to the interplay of a variety of intermolecular forces. Elucidating how the interactions within the chemically distinct partners influence the nanomechanical properties of the membrane is essential to gain a comprehensive understanding of a wide-variety of both force-triggered and force-sensing mechanisms that dictate essential cellular processes.


Assuntos
Membrana Celular/metabolismo , Bicamadas Lipídicas/metabolismo , Mecanotransdução Celular , Animais , Fenômenos Biomecânicos , Biofísica/métodos , Membrana Celular/química , Humanos , Bicamadas Lipídicas/química , Microscopia de Força Atômica/métodos
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