MOLECULAR SIMULATION OF AMPHIPHILE EFFECTS ON BIOLOGICAL MEMBRANE ELECTROSTATIC

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 水杨酸盐是一种两亲性分子，是非甾体抗炎药家族的一个重要成员，它通过降低耳外毛细胞的机电耦合作用而影响听力。水杨酸对耳朵外毛细胞的电活动性、形状和膜电容的影响的研究已经在实验上进行了。然而，水杨酸盐与生物膜相互作用的分子机制及其对外毛细胞电生理的影响仍然是未知的。我们的长期目标是建立外毛细胞的多尺度模型，以了解水杨酸盐与膜作用的分子机制及其对外毛细胞电生理学的影响。这一初步研究将为了解水杨酸和氯丙嗪等两亲性药物对生物膜性质的影响奠定基础，从而有助于阐明这些两亲性药物影响听力的分子机制。建议的工作将提供的结果进行比较，我们的合作者，博士威廉E。Brownell（Baylor Coll. Med.）罗伯特·拉斐尔（Rice University）

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. Salicylate, an amphiphilic molecule and a popular member of non-steroidal anti-inflammatory drug family, is known to affect hearing through reduction of the electromechanical coupling in the outer hair cells of the ear. Investigations into the effects of salicylate on electromotility, shape, and membrane capacitance of the outer hair cell of the ear have been pursued experimentally. However, the molecular mechanism of salicylate interaction with biological membranes and its effect on outer hair cell electrophysiology are still unknown. Our long term goal is to develop multiscale models of the outer hair cell in order to understand the molecular mechanism of salicylates action with the membrane and its effect on outer hair cell electrophysiology. This initial research will lay the groundwork for understanding the effect of amphiphilic drugs, such as salicylate and chlorpromazine, on the properties of biological membranes, and thereby help to elucidate the molecular mechanisms for these amphiphiles effects on the hearing ability. The proposed work will provide results to be compared to the experimental work of our collaborators, Drs. William E. Brownell (Baylor Coll. Med.) and Robert Raphael (Rice Univ.).