experimental-imaging-techniques-for-examining-fibrin-clot-structures

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Fibrin is an extracellular matrix protein that is responsible for maintaining the structural integrity of blood clots. Much research has been done on ...

Georgia Institute of Technology

We tested what to our knowledge is a new computational model for fibrin fiber mechanical behavior. The model is composed of three distinct elements: the folded fibrinogen core as seen in the crystal structure, the unstructured α-C connector, and the partially folded α-C domain. Previous studies have highlighted the importance of all three regions and how they may contribute to fibrin fiber stress-strain behavior. Yet no molecular model has been computationally tested that takes into account the individual contributions of all these regions. Constant velocity, steered molecular dynamics studies at 0.025 Å/ps were conducted on the folded fibrinogen core and the α-C domain to determine their force-displacement behavior. A wormlike chain model with a persistence length of 0.8 nm (Kuhn length = 1.6 nm) was used to model the mechanical behavior of the unfolded α-C connector. The three components were combined to calculate the total stress-strain response, which was then compared to experimental data. The results show that the three-component model successfully captures the experimentally determined stress-strain behavior of fibrin fibers. The model evinces the key contribution of the α-C domains to fibrin fiber stress-strain behavior. However, conversion of the α-helical coiled coils to β-strands, and partial unfolding of the protein, may also contribute.

A modular fibrinogen model that captures the stress-strain behavior of fibrin fibers.

In this study, a novel technique was developed in which magnetic microparticles (MMPs) and quantum dots (QDs) were successfully incorporated into fibrin clots. The MMPs were added at concentrations of 0.1 and 1 wt % of the fibrin content in an effort to determine if a magnetic field could be used to mechanically stretch the fibrin network, simulating how cells may invade a network. The QDs were added at a dilute concentration of 0.1 wt % to determine if the mechanical properties of the fibrin network would be significantly altered and to ascertain if the overall stretch on the network could be observed. Based on strain sweep and frequency sweep rheological analysis, it was determined that both QDs and MMPs incorporated into fibrin networks at 0.1 wt % caused irreversible plastic deformation in the fibrin clot sample, as evidenced by a precipitous decline in the storage modulus value.

Rodney D. Averett

Parker H. Petit Institute for Bioengineering & Bioscience,
George W. Woodruff School of Mechanical Engineering

Georgia Institute of Technology

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Rodney D. Averett

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Parker H. Petit Institute for Bioengineering & Bioscience,George W. Woodruff School of Mechanical Engineering

Georgia Institute of Technology

Experimental and Imaging Techniques for Examining Fibrin Clot Structures in Normal and Diseased States

Parker H. Petit Institute for Bioengineering & Bioscience,
George W. Woodruff School of Mechanical Engineering