Biomechanics of Actin Network Regulated by Physical Mechanisms

This program seeks to characterize physical properties of an essential type of protein filament, F-actin, and the network they form to mimic that in cells. The research aims at defining and assessing the interactions between the negatively charged protein filaments from two physical origins: orientational ordering and solution electrostatics. Specifically, experiments are planned to quantitatively determine the effects of phase transitions and weak electrostatic interactions on the morphology, motion, and rheological properties of F-actin under physiologically relevant concentrations. The planned research serves several related missions. From a biological perspective, it promotes understanding of the molecular properties and the physical principles that drive protein assembly and interactions. The knowledge acquired may lead to biomedical applications by manipulating properties related to protein aggregation. From the fundamental physics perspective, various interactions that are of physical nature will be quantitatively defined. The experimental data to be obtained will be crucial for testing predictions from theoretical treatments and computer simulations that are applicable to an important class of systems involving the hierarchical assembly of filamentous macromolecules. From a material science perspective, the insight acquired through this particular system of study is also useful for interpreting similar physical properties in other systems involving solutions or gels consisting of charged and semiflexible polymers. The program, therefore, contributes a general strategy to the characterization of a range of soft materials. Finally, the program provides training in multidisciplinary research at the interface between the nanoscale mechanics and biological science. A collaborative approach is taken to provide research opportunities to selected science students and teachers from local schools.

Project Report

This program was designed to characterize physical properties of an essential type of protein filament, F-actin, and the network they form to mimic that in cells. The research aimed at defining and assessing the interactions between the negatively charged protein filaments from two physical origins: orientational ordering and solution electrostatics. Specifically, experiments were planned to quantitatively determine the effects of phase transitions and weak electrostatic interactions on the morphology, motion, and rheological properties of F-actin under physiologically relevant concentrations. The planned research served several related missions. From a biological perspective, it promoted understanding of the molecular properties and the physical principles that drive protein assembly and interactions. The knowledge acquired was useful for manipulating properties related to protein aggregation. From the fundamental physics perspective, various interactions that are of physical nature were quantitatively defined. The experimental data obtained were used to test predictions from theoretical treatments and computer simulations that are applicable to an important class of systems involving the hierarchical assembly of filamentous macromolecules. From a material science perspective, the insight acquired through this particular system of study proved useful for interpreting similar physical properties in other systems involving solutions or gels consisting of charged and semiflexible polymers. The program, therefore, contributed a general strategy to the characterization of a range of soft materials. Finally, the program provided training of four graduate students and several undergraduates in multidisciplinary research at the interface between the nanoscale mechanics and biological science. A collaborative approach was taken to provide research opportunities to selected science students and teachers from local schools. Over the single funding cycle, the NSF grant led to publication of 4 original research papers plus a proceeding article at an NSF grantee conference. The four peer-reviewed papers each became an integral part of a PhD thesis. The research outputs contributed significantly to the evolving literature in the field, and the full impact is yet to be seen over the next few years as our publications are read and referred to by other researchers in their further studies.

Project Start
Project End
Budget Start
2008-09-01
Budget End
2012-08-31
Support Year
Fiscal Year
2008
Total Cost
$306,000
Indirect Cost
Name
Brown University
Department
Type
DUNS #
City
Providence
State
RI
Country
United States
Zip Code
02912