Busch N A, Yarmush M L, Toner M
Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, Boston, Massachusetts 02139 USA.
Biophys J. 1998 Dec;75(6):2956-70. doi: 10.1016/S0006-3495(98)77737-9.
The objective of this investigation was to examine, from a theoretical perspective, the mechanism underlying the lysis of plasma membranes by photoinduced, chemically mediated damage such as is found in photolysis. Toward this end, a model is presented which relates the membrane lifetime to the thermodynamic parameters of the membrane components based upon the kinetic theory of aggregate formation. The formalism includes a standard birth/death process for the formation of damaged membrane components (i.e., peroxidized lipids) as well as a terminating condensation process for the formation of aggregates of peroxidized plasma membrane lipids. Our theory predicts that 1) the membrane lifetime is inversely correlated with predicted rate of membrane damage; 2) an upper limit on the duration of membrane damage exists, above which the mean and variance of the membrane lifetime is independent of further membrane damage; and 3) both the mean and variance of the time of membrane lifetime distribution are correlated with the number of sites that may be damaged to form a single membrane defect. The model provides a framework to optimize the lysis of cell membranes by photodynamic therapy.
本研究的目的是从理论角度探讨光诱导化学介导损伤(如光解中发现的损伤)导致质膜裂解的潜在机制。为此,提出了一个模型,该模型基于聚集体形成的动力学理论,将膜寿命与膜成分的热力学参数联系起来。该形式体系包括受损膜成分(即过氧化脂质)形成的标准产生/死亡过程,以及过氧化质膜脂质聚集体形成的终止凝聚过程。我们的理论预测:1)膜寿命与预测的膜损伤速率呈负相关;2)膜损伤持续时间存在上限,超过该上限,膜寿命的均值和方差与进一步的膜损伤无关;3)膜寿命分布时间的均值和方差均与可能受损形成单个膜缺陷的位点数量相关。该模型为通过光动力疗法优化细胞膜裂解提供了一个框架。