The Mechanics of Silk-Elastin-Like Proteins

自然界一直是设计具有所需机械性能的新生物材料的刺激来源。例如，天然丝绸具有比钢铁更高的断裂韧性，而人类弹性蛋白是最持久和最具弹性的蛋白质之一，估计半衰期为70年。通过融合这两种蛋白的多肽序列，丝状弹性蛋白样蛋白(SELP)已被用于各种生物医学应用。在混合SELP中，丝状块可以结晶，提供机械强度，而弹性蛋白样块通过降低丝状块的结晶度来增强变形能力。通过控制丝素和弹性蛋白类块的长度和顺序以及调节结晶过程，可以在SELP中实现高机械强度和变形能力的结合。本研究的目的是了解SELP的基本变形机制，促进基于蛋白质的新材料的合理设计。为了实现这一目标，将对自结晶的热力学和动力学进行实验研究，并将表征其在生理相关条件下的变形。这项拟议的研究将为具有所需机械性能的新型蛋白质材料的分子设计和基因工程提供必要的第一步。将探索SELP在各种生物医学应用中的潜力，其中机械方面的考虑尤其相关。这项研究的结果也将被整合到本科和研究生课程中。进行这项研究的本科生和研究生，包括代表性不足的少数族裔和女性，将接受这些新兴的生物力学和生物材料领域的培训。

Nature has been a source of stimulation for the design of new biomaterials with desired mechanical properties. For example, native silk can possess a fracture toughness that is higher than that of steel, and human elastin is one of the most durable and resilient proteins with an estimated half-life of 70 years. By fusing polypeptide sequences derived from these two proteins, silk-elastin-like proteins (SELPs) have been genetically engineered for various biomedical applications. In the hybrid SELPs, the silk-like blocks can be crystallized, providing mechanical strength, while the elastin-like blocks enhance deformability by reducing crystallinity of the silk-like blocks. A combination of high mechanical strength and deformability could be achieved in a SELP by controlling the length and sequence of the silk- and elastin-like blocks and by regulating the crystallization process. The objective of this research is to understand the fundamental deformation mechanisms of SELPs, facilitating a rational design of new protein-based materials. To achieve this goal, the thermodynamics and kinetics of the SELP crystallization will be experimentally examined and its deformation under physiologically relevant conditions will be characterized. The proposed research will provide the necessary first step toward the molecular design and genetic engineering of new protein-based materials with desired mechanical properties. The potential of SELPs for various biomedical applications will be explored, where mechanical considerations are particularly relevant. Results from the research will be also integrated into a combined undergraduate and graduate course. Undergraduate and graduate students performing the research, including underrepresented minorities and women, will receive training in these emerging areas of biomechanics and biomaterials.