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

现代生物技术和生物医学依赖于将DNA和药物等正常情况下不透水的分子送入细胞。基因转移的物理方法依赖于暂时机械地破坏细胞质膜，以允许分子进入细胞。细胞膜是一个复杂的细胞结构。我们对与暂时的细胞通透性和细胞力学(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，可以暂时渗透贴壁细胞。这项技术利用惰性气体喷射产生的力量在细胞膜上形成临时的毛孔。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，以识别和改变生化和生理特性。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。孔的形成依赖于电池的机械性能将被调查。我们还将通过在其他实验装置中重新创建类似的力来验证临时孔隙形成的依赖性。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。这一研究计划的发现可以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新技术。

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.