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Published on: July 18, 2011
Blood coagulation protein binds to Ca2+-induced phosphatidylserine nanodomains as revealed by atomic force microscopy
Jie Cheng1, Junhong Lü2, Xueling Li3
1Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250000, China.
Abstract:
The interaction between coagulation factor VIII (FVIII) and phospholipid membranes is a critical aspect of the blood clotting process. While it is known that FVIII binds to negatively charged phospholipids, the role of calcium ions (Ca2+) in this process remains an area of ongoing research. This study investigated the dynamic effects of Ca2+ on FVIII binding to phospholipid membranes, in particular how Ca2+-induced nanodomain formation affects this interaction. Using in situ atomic force microscopy (AFM) imaging, we observed the morphological and structural changes of supported lipid bilayers (DPPC/DOPS and DOPC/DPPS systems) in response to Ca2+. The results showed that Ca2+ not only alters the membrane lipid structure, but also promotes the formation of nanodomain in the phosphatidylserine (PS)-enriched regions. In the presence of Ca2+, FVIII bound preferentially to PS nanodomains with height differences of about 0.8 nm compared to adjacent membrane regions, and the binding process was further facilitated by Ca2+-induced reorganization of the lipid phases over time scales of 40-230 min. These findings provided new insights into the molecular mechanisms governing the interaction of FVIII with phospholipid membranes and underlined the crucial role of Ca2+ in supporting the functional activity of coagulation protein.
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