CAREER: Revealing the Mechanism of Non-endocytotic CPP-modulated Protein Delivery

细胞穿透肽具有绕过细胞内吞摄取机制的非凡能力，并利用不依赖能量的途径直接运输到细胞质。这种细胞穿透肽还可以携带大的载货分子（蛋白质、DNA、纳米粒子）穿过细胞膜。然而，细胞穿透肽跨膜运输的机制已被证明是难以解决的。该项目采用先进的膜复制技术，系统地识别和量化细胞穿透肽特性背后的关键相互作用和力量。通过比较和对比细胞穿透肽在复制膜和活细胞中的摄取，本项目旨在阐明非内吞肽介导的转运机制。更广泛的影响。将开发一个教育工具包（MOST工具包）用于教授三个基本概念：膜，渗透和选择性运输。MOST工具包将成为马萨诸塞大学教授的课程模块的基础，以及马萨诸塞大学和波多黎各马亚圭斯大学本科生参与的同行指导交换研究项目的基础。

Cell-penetrating peptides possess the remarkable ability to bypass the endocytosis uptake mechanism of the cell and are transported directly to the cytoplasm utilizing an energy-independent pathway. Such cell-penetrating peptides can also carry large cargo molecules (proteins, DNA, nanoparticles) across a cell membrane. However, the mechanisms by which cell penetrating peptides are transported across membranes have proven difficult to resolve. This project employs an advanced membrane replica technique to systematically identify and quantify the key interactions and forces that underlie the properties of cell-penetrating peptides. By comparing and contrasting the uptake of cell penetrating peptides in replica membranes and in live cells this project aims to elucidate the mechanism of non-endocytotic peptide-mediated transport.Broader Impacts. An educational toolkit (the MOST kit) will be developed for use in teaching three fundamental concepts: Membranes, Osmosis and Selective Transport. The MOST kit will form the basis for course modules taught at the University of Massachusetts, and for peer-mentored exchange research programs engaging undergraduate students at the University of Massachusetts and the University of Puerto Rico Mayaguez.