Institute of Fundamental Technological Research
Polish Academy of Sciences

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R.G. Bacabac

FOM Institute AMOLF (NL)

Recent publications
1.  Jansen K.A., Bacabac R.G., Piechocka I.K., Koenderink G.H., Cells actively stiffen fibrin networks by generating contractile stress, BIOPHYSICAL JOURNAL, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2013.10.008, Vol.105, No.10, pp.2240-2251, 2013

Abstract:
During wound healing and angiogenesis, fibrin serves as a provisional extracellular matrix. We use a model system of fibroblasts embedded in fibrin gels to study how cell-mediated contraction may influence the macroscopic mechanical properties of their extracellular matrix during such processes. We demonstrate by macroscopic shear rheology that the cells increase the elastic modulus of the fibrin gels. Microscopy observations show that this stiffening sets in when the cells spread and apply traction forces on the fibrin fibers. We further show that the stiffening response mimics the effect of an external stress applied by mechanical shear. We propose that stiffening is a consequence of active myosin-driven cell contraction, which provokes a nonlinear elastic response of the fibrin matrix. Cell-induced stiffening is limited to a factor 3 even though fibrin gels can in principle stiffen much more before breaking. We discuss this observation in light of recent models of fibrin gel elasticity, and conclude that the fibroblasts pull out floppy modes, such as thermal bending undulations, from the fibrin network, but do not axially stretch the fibers. Our findings are relevant for understanding the role of matrix contraction by cells during wound healing and cancer development, and may provide design parameters for materials to guide morphogenesis in tissue engineering.

Affiliations:
Jansen K.A. - FOM Institute AMOLF (NL)
Bacabac R.G. - FOM Institute AMOLF (NL)
Piechocka I.K. - other affiliation
Koenderink G.H. - FOM Institute AMOLF (NL)
2.  Piechocka I.K., Bacabac R.G., Potters M., MacKintosh F.C., Koenderink G.H., Structural Hierarchy Governs Fibrin Gel Mechanics, BIOPHYSICAL JOURNAL, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2010.01.040, Vol.98, No.10, pp.2281-2289, 2010

Abstract:
Fibrin gels are responsible for the mechanical strength of blood clots, which are among the most resilient protein materials in nature. Here we investigate the physical origin of this mechanical behavior by performing rheology measurements on reconstituted fibrin gels. We find that increasing levels of shear strain induce a succession of distinct elastic responses that reflect stretching processes on different length scales. We present a theoretical model that explains these observations in terms of the unique hierarchical architecture of the fibers. The fibers are bundles of semiflexible protofibrils that are loosely connected by flexible linker chains. This architecture makes the fibers 100-fold more flexible to bending than anticipated based on their large diameter. Moreover, in contrast with other biopolymers, fibrin fibers intrinsically stiffen when stretched. The resulting hierarchy of elastic regimes explains the incredible resilience of fibrin clots against large deformations.

Affiliations:
Piechocka I.K. - other affiliation
Bacabac R.G. - FOM Institute AMOLF (NL)
Potters M. - Vrije Universiteit (NL)
MacKintosh F.C. - Vrije Universiteit (NL)
Koenderink G.H. - FOM Institute AMOLF (NL)

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