The Mechanics of Fibrin Networks and their Alterations by Platelets
Contributors: Weitz, David A.; Mahadevan, Lakshminarayanan; Manoharan, Vinothan
Published: 2013
Language: eng
Description: Fibrin is a biopolymer that assembles into a network during blood coagulation to become the structural scaffold of a blood clot. The precise mechanics of this network are crucial for a blood clot to properly stem the flow of blood at the site of vascular injury while still remaining pliable enough to avoid dislocation. A hallmark of fibrin's mechanical response is strain-stiffening: at small strains, its response is low and linear; while at high strains, its stiffness increases non-linearly with increasing strain. The physical origins of strain-stiffening have been studied for other biopolymer systems but have remained elusive for biopolymer networks composed of stiff filaments, such as fibrin. To understand the origins of this intriguing behavior, we directly observe and quantify the motion of all of the fibers in the fibrin networks as they undergo shear in 3D using confocal microscopy.

We show that the strain-stiffening response of a clot is a result of the full network deformation rather than an intrinsic strain-stiffening response of the individual fibers. We observe a distinct transition from a linear, low-strain regime, where all fibers avoid any internal stretching, to a non-linear, high-strain regime, where an increasing number of fibers become stretched. This transition is characterized by a high degree of non-affine motion. Moreover, we are able to precisely calculate the non-linear stress-strain response of the network by using the strains on each fiber measured directly with confocal microscopy and by assuming the fibers behave like linearly elastic beams. This result confirms that it is the network deformation that causes the strain-stiffening behavior of fibrin clots. These data are consistent with predictions for low-connectivity networks with soft, bending, or floppy modes.

Moreover, we show that the addition of small contractile cells, platelets, increases the low-strain stiffness of the network while the high-strain stiffness is independent of the presence of the platelets; this is also consistent with expectations for small contractile elements in a network with low connectivity. Our results elucidate the origins of strain-stiffening in fibrin networks as well as the mechanism underlying platelet-induced clot stiffening.
Notes: Keywords: confocal microscopy, floppy modes, low-connectivity network, rheology, stiff biopolymer, strain stiffening.

Thesis Ph.D. Harvard University 2013