Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

Foreman-Ortiz Isabel U.; Liang Dongyue; Laudadio Elizabeth D.Calderin Jorge D.Wu MengKeshri PuspamZhang XianzhiSchwartz Michael P.Hamers Robert J.Rotello Vincent M.Murphy Catherine J.Cui QiangPedersen Joel A.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

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Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

机译：Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

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Understanding the mechanisms of nanoparticle interaction with cell membranes is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing engineered nanomaterial safety. Much attention has focused on nanoparticles that bind strongly to biological membranes or induce membrane damage, leading to adverse impacts on cells. More subtle effects on membrane function mediated via changes in biophysical properties of the phospholipid bilayer have received little study. Here, we combine electrophysiology measurements, infrared spectroscopy, and molecular dynamics simulations to obtain insight into a mode of nanoparticle-mediated modulation of membrane protein function that was previously only hinted at in prior work. Electrophysiology measurements on gramicidin A (gA) ion channels embedded in planar suspended lipid bilayers demonstrate that anionic gold nanoparticles (AuNPs) reduce chan-nel activity and extend channel lifetimes without disrupting membrane integrity, in a manner consistent with changes in membrane mechanical properties. Vibrational spectroscopy indicates that AuNP interaction with the bilayer does not perturb the conformation of membrane-embedded gA. Molecular dynamics simulations reinforce the experimental findings, showing that anionic AuNPs do not directly interact with embedded gA channels but perturb the local properties of lipid bilayers. Our results are most consistent with a mechanism in which anionic AuNPs disrupt ion channel function in an indirect manner by altering the mechanical properties of the surrounding bilayer. Alteration of membrane mechanical properties represents a potentially important mechanism by which nanoparticles induce biological effects, as the function of many embedded membrane proteins depends on phospholipid bilayer biophysical properties.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2020年第45期|27854-27861|共8页
作者
Foreman-Ortiz Isabel U.; Liang Dongyue; Laudadio Elizabeth D.Calderin Jorge D.Wu MengKeshri PuspamZhang XianzhiSchwartz Michael P.Hamers Robert J.Rotello Vincent M.Murphy Catherine J.Cui QiangPedersen Joel A.;
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作者单位

Dept Chem,Univ Wisconsin;

Dept Chem,Univ Illinois;

Dept Chem,Univ MassachusettsDept Chem,Boston Univ;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
nanoparticle; ion channel; molecular dynamics; electrophysiology; phospholipid; LIPID-BILAYER; GOLD NANOPARTICLES; GRAMICIDIN-A; HYDROPHOBIC MISMATCH; PROTEIN FUNCTION; FORCE-FIELD; SURFACE; MODEL; CHARMM; DYNAMICS;

Anionic nanoparticle-induced perturbation to phospholipid membranes affects ion channel function

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