BIOPHYSICAL THEORY AND MODELING |
Measuring Forces between Protein Fibers by Microscopy
Christopher W Jones 1, Jiang Cheng Wang 2, Robin W. Briehl 2 and Matthew S Turner 1*
1 University of Warwick
2 Albert Einstein Col. of Med.
* To whom correspondence should be addressed. E-mail: m.s.turner{at}warwick.ac.uk.
Submitted on July 30, 2004
Revised on October 6, 2004
Accepted on 14 January 2005
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Abstract |
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We propose a general scheme for measuring the attraction between mechanically frustrated semi-flexible fibers by measuring their thermal fluctuations and shape. We apply this analysis to a system of sickle hemoglobin (HbS) fibers which laterally attract one-another. These fibers appear to 'zip' together before reaching mechanical equilibrium due to the existence of crosslinks into a dilute fiber network. We are also able to estimate the rigidities of the fibers. These rigidities are found to be consistent with sickle hemoglobin `single' fibers 20nm in diameter, in spite of recent experiments indicating that fiber bundling sometimes occurs. Our estimate of the magnitude of the inter-fiber attraction for HbS fibers is in the range 8+/-7kT/micron, or 4+/-3kT/micron if the fibers are assumed, a priori, to be single fibers (Such an assumption is fully consistent with the data). This value is sufficient to bind the fibers, overcoming entropic effects, although extremely chemically weak. Our results are compared to models for the inter-fiber attraction that include depletion and van der Waals forces. This technique should also facilitate a similar analysis of other filamenatous protein assembles in the future, including beta-amyloid, actin, tubulin.
Key Words:
fiber, hemoglobin, interaction, sickle
