尤物视频

Synopsis

Collagen emerged at the dawn of multicellular life as an essential building block of tissues. Our understanding has evolved from viewing collagen as merely a physical framework to recognizing it as a dynamic scaffold that regulates cellular responses through mechanotransduction. Intriguingly, collagen assembles into higher-order structures that provide mechanical support to tissues, despite being thermally unstable at body temperature. However, studies on collagen鈥檚 sequence, structure, and mechanics have primarily relied on short model peptides, which often fail to accurately represent native collagen sequences. Hence, there is a growing need for the development of new methods that enable the study of native collagen in its full-length context, offering insights into how it upholds its dynamic function despite its thermal instability. Using atomic force microscopy (AFM) imaging, I investigated collagen鈥檚 response to temperature and observed a time-dependent loss of folded protein at body temperature, including an overall shortening of the contour length, reflecting structural destabilization. I further characterized the bending stiffness profile of collagen IV as a function of temperature and identified a putative initiation site for thermally induced unfolding. My findings also revealed that interchain disulfide bonds enhance the thermal stability of collagen IV and serve as the primary nucleation site for in vitro refolding. Additionally, multiple sequence alignments across diverse species uncovered an evolutionarily conserved cystine knot present across metazoan phyla, underscoring its significance in early collagen IV structures. These results provide new insights into collagen鈥檚 thermal response and the first steps to establishing relations between its sequence-encoded information and mechanical properties in these large proteins.