期刊
CELLULAR AND MOLECULAR BIOENGINEERING
卷 3, 期 2, 页码 128-138出版社
SPRINGER
DOI: 10.1007/s12195-010-0110-6
关键词
Catch bonds; On-rate; Single molecule; Dynamic force spectroscopy
资金
- Department of Biomedical Engineering at the University of Virginia
- National Institutes of Health [EB002185]
- NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING [R01EB002185] Funding Source: NIH RePORTER
Molecular dissociation rates have long been known to be sensitive to applied force. We use a laser trap to provide evidence that rates of association may also be force-dependent. We use the thermal fluctuation assay to study single bonds between E-selectin and sialyl Lewis a (sLe(a)), the sugar on PSGL-1 to which the three selectins bind. Briefly, an E-selectin-coated bead is held in a laser trap and pressed with various compressive loads against the vertical surface of a bead coated with sLe(a). The time it takes for a bond to form is used to calculate a specific two-dimensional on-rate, k(on)(o): We observe an increase in k(on)(o) with increasing compressive force, providing single molecule evidence that on-rate, in addition to off-rate, is influenced by load. By measuring bond lifetimes at known tensile loads, we show that E-selectin, like its family members L-and P-selectin, is capable of forming catch bonds. Our data support a reverse Bell model, in which compressive forces lower the activation energy for binding. Load-dependent on-rates may be a general feature of all intermolecular bonds.
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