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Multi-Scale Modeling of Chemical-to-Mechanical Energy Conversion in Actin-Based Motility

Contents


Contact Information

Principal Investigator/Contact
Anthony Ladd
University of Florida
Phone: (352) 392-6509
Fax: (352) 392-9513
E-Mail: ladd@che.ufl.edu

Co-PIs and Collaborators
Richard Dickinson
University of Florida

Jason Butler
University of Florida

Daniel Purich
University of Florida

David Weitz
Harvard University

Grant Number - 505929

Funding Agency

National Science Foundation (NSF)

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Research Emphasis

The researchers propose to develop and validate a biologically relevant, multi-scale model of force generation by actin polymerization. In actin-based motility, monomeric actin polymerizes into stiff filaments from surface-bound components (such as the Listeria monocytogenes surface protein ActA), which crosslink and propel the surface forward. How the chemical energy involved in monomer addition is converted into mechanical work is critical in understanding cell motility, and for exploiting actin-based motility for micro-/nanoscale sensors and actuators.

The new model will enable the researchers to simulate the dynamics of stiff fibers, composed of many segments interacting thermodynamically and hydrodynamically. The projects also proposes a sequence of experimental validations; first, determination of the viscoelastic properties of actin gels using microrheological experiments developed, and second, measurement of force generation by the polymerizing network.

Actin is a globular protein that polymerizes helically forming actin filaments (or microfilaments), which like the other two components of the cellular cytoskeleton form a three-dimensional network inside an eukaryotic cell. Actin filaments provide mechanical support for the cell, determine the cell shape, enable cell movements; and participate in certain cell junctions, in cytoplasmic streaming and in contraction of the cell during cytokinesis. In muscle cells they play an essential role, along with myosin, in muscle contraction.

A monomer is a small molecule that may become chemically bonded to other monomers to form a polymer.

Polymerization is a process of reacting monomer molecules together in a chemical reaction to form linear chains or a three-dimensional network of polymer chains.

Cell motility is the ability of a cell to move.

Hydrodynamics is the study of fluid motion.

Thermodynamics is the branch of physics concerned with the conversion of different forms of energy. 

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Scales Examined 

Time Scales

  • Microsecond (μs)
  • Millisecond (ms)
  • Second(s)
  • Minutes
  • Hours
  • Days
  • Months
  • Years and above

Biological Scales

  • Molecular
  • Molecular Complexes
  • Sub-Cellular
  • Cellular

Length Scales 

  • Micrometer (μm)
  • Millimeter (mm)
  • Centimeter (cm)
  • Ten centimeter

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Biomedical, Biological and Behavioral (BBB) Areas and Percent Focus

60% - Actin polymerization; mechanics of cytoskeleton, bacterial propulsion

Modeling Methods and Tools (MMT)Areas and Percent Focus

Numerical simulations of solutions of chemically functionalized biopolymers  

Software Development

Languages and Tools

New algorithms for efficient simulations of polymer solutions.

 

 

 

 

Last reviewed on: 12/21/2006

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