NANOINJECTION OF MEMBRANES: FORCES AND MOLECULAR MECHANISMS

膜的纳米注射：力和分子机制

• 批准号: 8171910
• 负责人: FRANCO MARIO CAPALDI
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171910
• 关键词: Carbon; Cell Survival; Cell membrane; Cells; Chemistry; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Dependence; Dimensions; Free Energy; Funding; Grant; Injection of therapeutic agent; Institution; Mechanics; Membrane; Molecular; Motion; Needles; Penetration; Pharmacologic Substance; Process; Research; Research Personnel; Resources; Scientist; Source; Structure; United States National Institutes of Health; molecular dynamics; nano; nanomedicine; simulation; Carbon; Cell Survival; Cell membrane; Cells; Chemistry; Cholesterol; Computer Retrieval of Information on Scientific Projects Database; Dependence; Dimensions; Free Energy; Funding; Grant; Injection of therapeutic agent; Institution; Mechanics; Membrane; Molecular; Motion; Needles; Penetration; Pharmacologic Substance; Process; Research; Research Personnel; Resources; Scientist; Source; Structure; United States National Institutes of Health; molecular dynamics; nano; nanomedicine; simulation

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. With the advent of nano-needles, and their use in nanomedicine, scientists are able to inject small quantities of pharmaceuticals into a single cell. It is theorized that the small dimensions of the needle minimize membrane disruption and do not compromise the viability of the cells themselves. However, we require a fundamental understanding of the mechanisms activated during injection, and the magnitude of cell disruption due to needle size and chemistry of both the needle and the membrane. The carbon nanotube is an excellent choice for molecular needle due to its mechanical integrity and long aspect ratio. We propose to expand on our studies of cell membrane penetration using Molecular Dynamics. Due to computational limitations, our previous studies focused on a penetration rate that was faster than some of the underlying dynamical processes. From these simulations, we were able to determine force-displacement curves, free energies of interaction, and study the molecular motion in the membrane induced by penetration. By varying the rate of indentation, we hope to probe the rate dependence of both the forces and mechanisms involved in this process. In addition, effects of membrane chemistry will be probed. At first, this will involve the penetration of cholesterol containing membranes and later this can be expanded to study penetration of membranes of varying composition and structure.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 随着纳米针的出现及其在纳米医学中的使用，科学家能够将少量药品注入单个细胞中。从理论上讲，针的小尺寸最小化膜破坏，不会损害细胞本身的生存能力。但是，我们需要对注射过程中激活的机制以及由于针头和膜的化学性质而导致的细胞破坏大小。由于其机械完整性和长宽比，碳纳米管是分子针的绝佳选择。我们建议使用分子动力学扩展对细胞膜渗透的研究。由于计算局限性，我们以前的研究集中在渗透率上，该速率比某些基本动力学过程快。从这些模拟中，我们能够确定力置换曲线，相互作用的自由能，并研究通过穿透引起的膜中的分子运动。通过改变凹痕率，我们希望探究此过程中涉及的力和机制的速率依赖性。此外，还将探测膜化学的作用。首先，这将涉及含有膜的胆固醇的渗透，后来可以扩展到研究不同组成和结构的膜的渗透。