This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cell migration is a superb example of biological complexity, as it intertwines biochemical signaling networks with biophysical locomotory processes. While the myriad of molecular components and interactions continue to become identified, the challenge looms to integrate them all into the operation of cell migration as a dynamical system. We are using the Virtual Cell (VC) environment to enable simulations of the locomotory process. The VC is already able to simulate reaction-diffusion equations on the 3-D domains (cellular interior) of complex geometries. Thus, numerical simulation and visualization of a sub-model are being developed that incorporate spatio-temporal dynamics of essential regulatory molecules in the cytoplasm. This includes reaction-diffusion equations describing chemical kinetics, diffusion and transport of actin monomers, actin binding proteins and ions. As the next step, we are enabling VC to solve the reaction-advection-diffusion equations of cytoskeletal mechanics and adhesive system on the 3-D domains and their boundaries, respectively. In addition to incorporating the appropriate numerics infrastructure to deal with the new mathematical formalisms, a key challenge will be to develop graphical representations of the biophysics that can be deployed by the user to fully specify models within a mechanics-enabled problem domain. Such representations would be structured in terms of easily manipulatable sets of components consisting of the structures, molecules, and relevant interactions. Finally, we will expand the VC software in order to dynamically change the cellular geometry to account for the protrusion/retraction movements of the cellular surface. We will adapt finite element techniques to problems of cytoskeletal dynamics with changing geometries.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR013186-14
Application #
8362486
Study Section
Special Emphasis Panel (ZRG1-CB-L (40))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
14
Fiscal Year
2011
Total Cost
$52,720
Indirect Cost
Name
University of Connecticut
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Ron, Amit; Azeloglu, Evren U; Calizo, Rhodora C et al. (2017) Cell shape information is transduced through tension-independent mechanisms. Nat Commun 8:2145
Novak, Igor L; Slepchenko, Boris M (2014) A conservative algorithm for parabolic problems in domains with moving boundaries. J Comput Phys 270:203-213
Semenova, Irina; Ikeda, Kazuho; Resaul, Karim et al. (2014) Regulation of microtubule-based transport by MAP4. Mol Biol Cell 25:3119-32
Michalski, Paul J (2014) First demonstration of bistability in CaMKII, a memory-related kinase. Biophys J 106:1233-5
Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John et al. (2014) Interconnected network motifs control podocyte morphology and kidney function. Sci Signal 7:ra12
Dickson, Eamonn J; Falkenburger, Björn H; Hille, Bertil (2013) Quantitative properties and receptor reserve of the IP(3) and calcium branch of G(q)-coupled receptor signaling. J Gen Physiol 141:521-35
Michalski, P J (2013) The delicate bistability of CaMKII. Biophys J 105:794-806
Falkenburger, Björn H; Dickson, Eamonn J; Hille, Bertil (2013) Quantitative properties and receptor reserve of the DAG and PKC branch of G(q)-coupled receptor signaling. J Gen Physiol 141:537-55
Ditlev, Jonathon A; Mayer, Bruce J; Loew, Leslie M (2013) There is more than one way to model an elephant. Experiment-driven modeling of the actin cytoskeleton. Biophys J 104:520-32
Acker, Corey D; Loew, Leslie M (2013) Characterization of voltage-sensitive dyes in living cells using two-photon excitation. Methods Mol Biol 995:147-60

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