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Tuning the Local Availability of VEGF within Glycosaminoglycan-Based Hydrogels to Modulate Vascular Endothelial Cell Morphogenesis
2020, Limasale, Yanuar Dwi Putra, Atallah, Passant, Werner, Carsten, Freudenberg, Uwe, Zimmermann, Ralf
Incorporation of sulfated glycosaminoglycans (GAGs) into cell-instructive polymer networks is shown to be instrumental in controlling the diffusivity and activity of growth factors. However, a subtle balance between local retention and release of the factors is needed to effectively direct cell fate decisions. To quantitatively unravel material characteristics governing these key features, the GAG content and the GAG sulfation pattern of star-shaped poly(ethylene glycol) (starPEG)–GAG hydrogels are herein tuned to control the local availability and bioactivity of GAG-affine vascular endothelial growth factor (VEGF165). Hydrogels containing varying concentrations of heparin or heparin derivatives with different sulfation pattern are prepared and thoroughly characterized for swelling, mechanical properties, and growth factor transport. Mathematical models are developed to predict the local concentration and spatial distribution of free and bound VEGF165 within the gel matrices. The results of simulation and experimental studies concordantly reveal how the GAG concentration and sulfation pattern determine the local availability of VEGF165 within the cell-instructive hydrogels and how the factor—in interplay with cell-instructive gel properties—determines the formation and spatial organization of capillary networks of embedded human vascular endothelial cells. Taken together, this study exemplifies how mathematical modeling and rational hydrogel design can be combined to pave the way for precision tissue engineering. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Correlations in multithermostat Brownian systems with Lorentz force
2020, Abdoli, Iman, Kalz, Erik, Vuijk, Hidde D., Wittmann, René, Sommer, Jens-Uwe, Brader, Joseph M., Sharma, Abhinav
We study the motion of a Brownian particle subjected to Lorentz force due to an external magnetic field. Each spatial degree of freedom of the particle is coupled to a different thermostat. We show that the magnetic field results in correlation between different velocity components in the stationary state. Integrating the velocity autocorrelation matrix, we obtain the diffusion matrix that enters the Fokker-Planck equation for the probability density. The eigenvectors of the diffusion matrix do not align with the temperature axes. As a consequence the Brownian particle performs spatially correlated diffusion. We further show that in the presence of an isotropic confining potential, an unusual, flux-free steady state emerges which is characterized by a non-Boltzmann density distribution, which can be rotated by reversing the magnetic field. The nontrivial steady state properties of our system result from the Lorentz force induced coupling of the spatial degrees of freedom which cease to exist in equilibrium corresponding to a single-temperature system. © 2020 The Author(s). Published by IOP Publishing Ltd on behalf of the Institute of Physics and Deutsche Physikalische Gesellschaft.