Conference proceeding
Developing a hybrid mesoscale model to predict the impact of oxidative stress damage to individual microtubules on overall cytoskeletal mechanics
2006 Bio Micro and Nanosystems Conference, pp 77-77
Jan 2006
Abstract
Recent experimental evidence has shown that cigarette smoke metal-catalyzed oxidation of tubulin causes microtubule depolymerization, which can result in endothelial cell contraction and vessel wall breakdown (FASEB J. 19:1096, 2005). This may be a mechanism for cigarette smoke enhancement of deleterious health effects of inflammatory disease. To understand how stochastic damage at the microscale level can translate to global properties of cell mechanics, we have developed an integrated mesoscale model of individual microtubule dynamics to predict and overall dynamics and mechanical properties of the cytoskeleton. Our model is founded on previously developed models of aspects of microtubule properties and parameters from published experimental data. The majority of existing individual microtubule models were developed to study dynamic instability, and they use the mean-field approach calculating the microtubule assembly and disassembly probability distributions. Based on this approach, we employ a Monte Carlo simulation of individual microtubules growing and shrinking in time and 3D spatial domains. Published models based on experimental evidence are used to incorporate microtubule bending, forces on individual microtubules, and the relationship between force and velocity into our hybrid model, resulting in a coupled stochastic and deterministic simulation. To calculate global mechanical properties of the cytoskeleton, multiple microtubules are simultaneously simulated in a random network and passively connected by "virtual" actin filaments, and the kinetic and potential energies of the overall configuration are dynamically computed using results from the tensegrity theory. We are validating our model by simulating the effect of taxol on microtubules and comparing our results with experimental data. The model is able to duplicate experimental observations (Mol. Biol. Cell 10:947, 1999) on the effect of taxol increasing rescue frequency, decreasing microtubule growth and shrinkage velocity, and strongly increasing pause frequency, percentage and duration. We are currently simulating the ability of taxol and other drugs to compensate for microtubule depolymerization due to oxidative stress, and consequently stabilizing the overall cytoskeletal structure. We are also comparing the predictions of our model to simultaneous experimental measurements of microtubule network dynamics in cultured cells transfected with GFP-tubulin and cell mechanics measured by atomic force microscopy (AFM)
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Details
- Title
- Developing a hybrid mesoscale model to predict the impact of oxidative stress damage to individual microtubules on overall cytoskeletal mechanics
- Creators
- H Zhao - Drexel UniversityB.A Sokhansanj - Drexel UniversityIEEE
- Publication Details
- 2006 Bio Micro and Nanosystems Conference, pp 77-77
- Conference
- 2006 Bio Micro and Nanosystems Conference
- Publisher
- The Institute of Electrical and Electronics Engineers, Inc. (IEEE)
- Number of pages
- 1
- Resource Type
- Conference proceeding
- Language
- English
- Academic Unit
- Electrical and Computer Engineering
- Web of Science ID
- WOS:000246328700042
- Other Identifier
- 991019170349204721
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Nanoscience & Nanotechnology