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Biomechanics of the Cell Plasma Membrane: The effect of shear stress and cell stiffness on temporary cell permeabilization

细胞质膜的生物力学：剪切应力和细胞刚度对临时细胞透化的影响

基本信息

批准号：
261938-2013
负责人：
Leask, Richard
金额：
$ 2.55万
依托单位：
McGill University
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2017
资助国家：
加拿大
起止时间：
2017-01-01 至 2018-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=638104
关键词：
Biomechanics Cell Plasma Membrane effect

项目摘要

Modern biotechnology and biomedicine are dependent on passing normally impermeable molecules like DNA and drugs into cells. Physical methods of gene transfer rely on mechanically disrupting the cell plasma membrane, temporarily, to allow the transport of molecules into the cell. The cell plasma membrane is a complex cell structure. We understand very little about the physical forces associated with temporary permeabilization and mechanics of the cell (biomechanics). Recently my lab has discovered a simple physical method to temporarily permeabilize adherent cells. This technique uses the forces created by an inert jet of gas to create temporary pores in the cell plasma membrane. The long term objective of my research program is to be able to quantify and manipulate the biomechanical properties of the cell to identify and change biochemical and physiologic properties. Over the next 5 years my laboratory will further develop our gas jet method and use it to understand the biomechanics of the cell plasma membrane. We will use computer simulations and flow visualization experiments to define the forces created by our device. The dependence of pore formation on the mechanical properties of the cell will be investigated. We will also validate the dependency of temporary pore formation by recreating similar forces in other experimental setups. The research will further develop a simple, inexpensive method for transferring genes and other macromolecules into cells without the need for viral vectors or cytotoxic drugs. The discoveries of this research program could be used to improve yields in biotech industries and provide researchers with new tools and techniques to study cell biology.

现代生物技术和生物医学依赖于将通常不可渗透的分子如DNA和药物传递到细胞中。基因转移的物理方法依赖于暂时性地机械破坏细胞质膜，以允许分子运输到细胞中。细胞质膜是一种复杂的细胞结构。我们对与细胞暂时渗透和力学（生物力学）相关的物理力知之甚少。最近我的实验室发现了一种简单的物理方法来暂时渗透粘附细胞。该技术利用惰性气体射流产生的力在细胞质膜上形成临时孔。我的研究计划的长期目标是能够量化和操纵细胞的生物力学特性，以识别和改变生物化学和生理特性。在接下来的5年里，我的实验室将进一步发展我们的气体喷射方法，并使用它来了解细胞质膜的生物力学。我们将使用计算机模拟和流动可视化实验来定义我们的设备所产生的力。将研究孔形成对细胞的机械性能的依赖性。我们还将通过在其他实验装置中重现类似的力来验证临时孔形成的依赖性。这项研究将进一步开发一种简单、廉价的方法，将基因和其他大分子转移到细胞中，而不需要病毒载体或细胞毒性药物。该研究计划的发现可用于提高生物技术行业的产量，并为研究人员提供研究细胞生物学的新工具和技术。