Transition Temperature in Cell Membranes Predicts Effectiveness of Cancer Drugs Erlotinib and Trail

Abstract

Lipids appear in cell membranes in various phases including Liquid ordered (Lo), Liquid disordered (Ld) and gel phase. As temperature varies, their distribution within cell membranes changes. Near a certain temperature in giant plasma membrane vesicle model membranes, the lipid distribution experiences critical behavior that can be modeled through the Ising model of magnetic spins. At temperatures above the critical temperature, lipid distribution is uniform. Below it, large domains of same lipid order aggregate, so we call it a transition temperature. Different cell types have different transition temperatures, and treating membranes with different chemicals also affects the transition temperature. Two cancer drugs, Erlotinib and Trail, were examined to view their impact on human cell membranes. Results indicate that Erlotinib does not affect membrane order, while Trail lowers the transition temperature. It was predicted that cells with a lower transition temperature would be more likely to undergo apoptosis (programmed cell death) after treatment with cancer drugs. An experiment was performed to see whether lowering the transition temperature of live human cells using a chemical (isopropanol) which does not induce apoptosis would make them more susceptible to the drug Erlotinib. Results indicated cells treated with isopropanol were more likely to be killed by Erlotinib than those without treatment. Since Trail lowers transition temperature and is effective at inducing apoptosis, the author set up several experiments using the drug to determine what the connection between transition temperature and ability to induce apoptosis might be. Those experiments are left for future research.