Recently it has been reported that actin filaments and microtubules are able to transmit electric signals and sustain ionic conductance. Since the velocity of electrical signals along these filaments is, depending on specific conditions, of same range as the propagation of neural impulses, the concurrent propagation of electrical signals along these filaments and electrochemical currents along the axonal membrane is possible in principle. This novel conduction mechanism observed in cells opens unexplored frontiers that will change the current understanding of neural activities and neuronal networks. Not surprisingly, the ionic conduction of these structures has been associated with processes as diverse as directional growth, cytotoxicity, plasticity, and migration. However, the underlying biophysical principles that support this behavior are poorly understood. Therefore, the objective of this proposed research is to generate substantial preliminary results to advance the molecular understanding of ionic conductance and electric signal transmission properties of microtubules and actin filaments. We believe that filaments and axon membranes may be able to transmit different kinds of information. Such capability may be affected by age and physiological conditions in different manner and therefore the corresponding propagation of electrical signal along filaments and neural axon membrane might be associated to different neural activity dysfunctions. Without question, investigating the biophysical principles underlying the electric and solvation properties of these cable-like filaments can bring an urgently needed progress in the molecular causes of many developmental and degenerative brain disorders. We may not validate our hypothesis and address this gap in knowledge using conventional models and approaches. Therefore one of the aims of this project consists in developing a computational tool to rationally investigate the electrophysiological mechanisms that affect conformational changes and conductance of electrical signals in both extra- and intracellular environments. We will perform a systematic characterization of these properties at a molecular level. This theoretical framework would also make great contributions to conventional areas of biochemistry where electrostatics underlies a major part of molecular properties. The proposed computational model will be then further extended to produce the mathematical engine to investigate signal transduction in proteins. The outcomes of this proposal will have a significant impact on the understanding and clinical applications of non-neuronal signal transduction and could open new therapeutic avenues to help the millions of patients currently affected by these disorders. In addition, the computational model (which will be publicly available) will enable the advancement of various technological and biomedical applications involving electrical conductance in proteins such as electrochemical biosensors, electric stimulation of tissue growth, and biomolecular processors.

Public Health Relevance

A number of recent biophysical studies demonstrate that actin filaments and microtubules are capable of sustaining ionic conductance and transmitting electric signals, thereby acting as 'electric cables', however, the underlying biophysical principles that support this behavior is poorly understood. The overall the objective of this proposal is to develop a comprehensive model to investigate the 'cable-like' behavior of actin filaments and microtubules. The outcomes of this proposal will have a significant impact on the understanding and clinical applications of non-neuronal signal transduction and intracellular information processing, electrical conductance in biosensors, the directed development of tissues (bone), and the development of biomolecular processors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Pilot Research Project (SC2)
Project #
1SC2GM112578-01
Application #
8795066
Study Section
Special Emphasis Panel (ZGM1-TWD-3 (SC))
Program Officer
Wehrle, Janna P
Project Start
2015-01-15
Project End
2018-01-14
Budget Start
2015-05-01
Budget End
2016-01-31
Support Year
1
Fiscal Year
2015
Total Cost
$147,000
Indirect Cost
$47,000
Name
University of Texas Health Science Center San Antonio
Department
Physics
Type
Schools of Arts and Sciences
DUNS #
800189185
City
San Antonio
State
TX
Country
United States
Zip Code
78249
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