During the last stage of cell division, cytokinesis, cells undergo a dramatic change in morphology as they rearrange themselves so as to produce two identical daughter cells. A detailed understanding of how these processes are regulated requires a fundamental knowledge of how different cytoskeletal proteins are spatially and temporally regulated, and how the resultant heterogeneity affects the mechanical properties of the cell. The complexity of these processes makes it nearly impossible to understand without a modeling framework that allows in silico testing of ideas and conceptual models. To elucidate the mechanisms by which cells regulate cytokinesis we need to appreciate how regulation of biochemical signaling cues effect changes in cell morphology. We will develop a suitable computational framework for studying the way in which biochemical regulation of cytoskeletal proteins results in desired cellular deformations during cytokinesis. Our simulations will be used to integrate computational modeling with quantitative measurements of the temporal and spatial changes of different proteins and the associated changes in cell shape during cytokinesis. Specifically, we propose: 1. to develop a computational framework for simulating whole cell, cell shape changes during mitosis;2. to develop an agent-based model of the actin cytoskeleton using a discrete-network representation of interacting filaments, and to use this model to investigate cell morphological changes during cytokinesis.

Public Health Relevance

Successful cell division has long been appreciated as critical to human health. Many cancer- associated genes lead to mitotic and/or cytokinetic failure. In this research we combine computational and experimental tools to study the way that cells regulate their mechanical properties to ensure that each mother cells successfully divides into two equally-sized daughter cells.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Modeling and Analysis of Biological Systems Study Section (MABS)
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Lyster, Peter
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Johns Hopkins University
Engineering (All Types)
Schools of Engineering
United States
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Luo, Tianzhi; Mohan, Krithika; Iglesias, Pablo A et al. (2013) Molecular mechanisms of cellular mechanosensing. Nat Mater 12:1064-71
Zheng, Yixian; Iglesias, Pablo A (2013) Nucleating new branches from old. Cell 152:669-70
Huang, Chuan-Hsiang; Tang, Ming; Shi, Changji et al. (2013) An excitable signal integrator couples to an idling cytoskeletal oscillator to drive cell migration. Nat Cell Biol 15:1307-16
Shi, Changji; Huang, Chuan-Hsiang; Devreotes, Peter N et al. (2013) Interaction of motility, directional sensing, and polarity modules recreates the behaviors of chemotaxing cells. PLoS Comput Biol 9:e1003122
Shi, Changji; Iglesias, Pablo A (2013) Excitable behavior in amoeboid chemotaxis. Wiley Interdiscip Rev Syst Biol Med 5:631-42
Porter, Joshua R; Burg, John S; Espenshade, Peter J et al. (2012) Identifying a static nonlinear structure in a biological system using noisy, sparse data. J Theor Biol 300:232-41
Luo, Tianzhi; Mohan, Krithika; Srivastava, Vasudha et al. (2012) Understanding the cooperative interaction between myosin II and actin cross-linkers mediated by actin filaments during mechanosensation. Biophys J 102:238-47
Kee, Yee-Seir; Ren, Yixin; Dorfman, Danielle et al. (2012) A mechanosensory system governs myosin II accumulation in dividing cells. Mol Biol Cell 23:1510-23
Mohan, Krithika; Iglesias, Pablo A; Robinson, Douglas N (2012) Separation anxiety: stress, tension and cytokinesis. Exp Cell Res 318:1428-34
Poirier, Christopher C; Zheng, Yixian; Iglesias, Pablo A (2010) Mitotic membrane helps to focus and stabilize the mitotic spindle. Biophys J 99:3182-90

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