Multiscale Modeling in Biology

Dr. Mark Alber, Departments of Mathematics and Physics, Interdisciplinary Center for the Study of Biocomplexity, University of Notre Dame

Multiscale modeling approach typical of systems biology tends to mix continuous, discrete, deterministic, and probabilistic submodels. We will discuss two examples of biological applications of this approach in the talk.

Swarming, a collective motion of many thousands of cells, produces colonies that rapidly spread over surfaces. In the second half of the talk a detailed cell- and behavior-based computational model of M. xanthus swarming will be used to show that  reversals of gliding direction are essential for swarming and that the reversal period predicted to maximize the swarming rate is the same as the period observed in experiments [1]. This suggests that the circuit regulating reversals evolved to its current sensitivity under selection for growth achieved by swarming. Also, an orientation correlation function will be used to show that microscopic social interactions help to form the ordered collective motion observed in swarms.

To prevent the loss of blood following a break in blood vessels, components in blood and the vessel wall interact rapidly to form a thrombus (clot) to limit hemorrhage. In this talk we will describe a multiscale model of thrombus formation consisting of components for modeling viscous, incompressible blood plasma; coagulation pathway; quiescent and activated platelets; blood cells; activating chemicals; fibrinogen; the vessel walls and their interactions. Model has been tested for robustness with respect to fluctuations of basic parameters [2]. Simulation results demonstrate the development of an inhomogeneous internal structure of the thrombus which was confirmed by the preliminary experimental data. Also, the dependence of the thrombus size on the blood flow rate in simulations is close to the one observed experimentally [3].  As heterogeneous structural domains within the clot affect thrombus stability, understanding the factors influencing thrombus structure is of significant biomedical importance.


1. Wu, Y., Jiang, Y., Kaiser, D., and M. Alber [2009], Periodic reversal of direction allows Myxobacteria to swarm, Proc. Natl. Acad. Sci. USA 106 4 1222-1227 (featured in the Nature News, January 20th, 2009, doi:10.1038/news.2009.43).

2. Xu, Z., Chen, N., , Kamocka, M.M., Rosen, E.D., and M.S. Alber [2008], Multiscale Model of Thrombus Development, Journal of the Royal Society Interface 5, 705-722.

3. Xu, Z., Chen, N., Shadden, S., Marsden, J.E., Kamocka, M.M., Rosen, E.D., and M.S. Alber [2009], Study of Blood Flow Impact on Growth of Thrombi Using a Multiscale Model, Soft Matter 5, 769-779.