Fibrinogen conformations and charge in electrolyte solutions derived from DLS and dynamic viscosity measurements
Journal of Colloid and Interface Science, ISSN: 0021-9797, Vol: 385, Issue: 1, Page: 244-257
2012
- 63Citations
- 59Captures
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Metrics Details
- Citations63
- Citation Indexes63
- 63
- CrossRef51
- Captures59
- Readers59
- 59
Article Description
Hydrodynamic properties of fibrinogen molecules were theoretically calculated. Their shape was approximated by the bead model, considering the presence of flexible side chains of various length and orientation relative to the main body of the molecule. Using the bead model, and the precise many-multipole method of solving the Stokes equations, the mobility coefficients for the fibrinogen molecule were calculated for arbitrary orientations of the arms whose length was varied between 12 and 18 nm. Orientation averaged hydrodynamic radii and intrinsic viscosities were also calculated by considering interactions between the side arms and the core of the fibrinogen molecule. Whereas the hydrodynamic radii changed little with the interaction magnitude, the intrinsic viscosity exhibited considerable variation from 30 to 60 for attractive and repulsive interactions, respectively. These theoretical results were used for the interpretation of experimental data derived from sedimentation and diffusion coefficient measurements as well as dynamic viscosity measurements. Optimum dimensions of the fibrinogen molecule derived in this way were the following: the contour length 84.7 nm, the side arm length 18 nm, and the total volume 470 nm 3, which gives 16% hydration (by volume). Our calculations enabled one to distinguish various conformational states of the fibrinogen molecule, especially the expanded conformation, prevailing for pH < 4 and lower ionic strength, characterized by high intrinsic viscosity of 50 and the hydrodynamic radius of 10.6 nm. On the other hand, for the physiological condition, that is, pH = 7.4 and the ionic strength of 0.15 M NaCl, the semi-collapsed conformation dominates. It is characterized by the average angle equal to < φ > = 55°, intrinsic viscosity of 35, and the hydrodynamic radius of 10 nm. Additionally, the interaction energy between the arms and the body of the molecule was predicted to be −4 kT units, confirming that they are oppositely charged than the central nodule. Results obtained in our work confirm an essential role of the side chains responsible for a highly anisotropic charge distribution in the fibrinogen molecule. These finding can be exploited to explain anomalous adsorption of fibrinogen on various surfaces.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S0021979712007618; http://dx.doi.org/10.1016/j.jcis.2012.07.010; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84865480720&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/22883236; https://linkinghub.elsevier.com/retrieve/pii/S0021979712007618; https://dx.doi.org/10.1016/j.jcis.2012.07.010
Elsevier BV
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