Restricted Research - Award List, Note/Discussion Page

Fiscal Year: 2018

1985  The University of Texas at San Antonio  (75803)

Principal Investigator: Marucho, Marcelo (Principal Investigator)  

Total Amount of Contract, Award, or Gift (Annual before 2011): $ 1,486,946

Exceeds $250,000 (Is it flagged?): Yes

Start and End Dates: 1/1/19 - 12/31/22

Restricted Research: YES

Academic Discipline: COS PHYSICS & ASTRONOMY  

Department, Center, School, or Institute: COS PHYSICS & ASTRONOMY  

Title of Contract, Award, or Gift: Polyelectrolyte Nature of Cytoskeleton Filaments

Name of Granting or Contracting Agency/Entity: NIH Natl Inst General Medical Sci
CFDA Link: HHS
93.859

Program Title: N/A
CFDA Linked: Biomedical Research and Research Training

Note:

Dysfunctions and malformations in Actin filaments (F-actins) and/or microtubules (MTs) are associate d with muscular (cardiomyopathies, skeletal myopathies), neurodegenerative, and deafness diseases. F-actins and MTs are highly charged rod-like cytoskeleton polyelectrolytes which transmit electric signals, sustain ionic conductance and overcome electrostatic interactions to form higher-order structures (bundles and networks). The basis for these filaments to form higher-order structures and enhance their electrical properties appears primarily or exclusively dominated by electrostatic interactions between monomers rather than their tertiary chemical structures. However, the underlying biophysical principles that support the polyelectrolyte nature of MTs and F-actin and anomalies on their biological functions associated with aging and inheritance conditions are still poorly understood. Because the concurrent propagation of electrical signals along cytoskeleton filaments and electrochemical currents along axonal membranes may transmit different kinds of information depending on the propagation medium and the physiological conditions, it is crucial to generate substantial results to advance the understanding of the molecular mechanisms governing the electrical signal propagation (bionanowire) and bundling formation properties of MTs and F-actin under different conditions. Recent preliminary data on F-actin in normal conditions reveal that a nontrivial balance and competition between the electric potential, water crowding, and ionic electrostatic screening correlation mechanisms are responsible for the stability, bundling and conducting properties of these filaments. Thus, molecular or cellular alterations often evident in pathological conditions is expected to break down this balance and competition leading to abnormalities in the bundling and bionanowire properties of these cytoskeleton filaments. The overall goal of this research proposal is to determine the impact of excessive alterations in the intracellular environment, significant differences on each subunit charge (ATP versus ADP in globular actin, GTP versus GDP in tubulin), and variations in the filament charge produced by isoforms and mutations on the polyelectrolyte properties of cytoskeleton filaments and their biological functions. Investigating this novel electrical conduction and bundling mechanisms observed in cells opens unexplored frontiers that will bring an urgently needed progress in the understanding and treatment of many developmental and degenerative disorders. In addition, the computational model along with a graphical user interface will be publicly available to enable non-experts in the field the characterization of charged filaments with relevance in broad areas of biochemistry and biomedicine. Further outcomes involve the use of these bionanowires in the advancement of technological and biomedical applications such as bionanosensors and computing bionanoprocessors.

Discussion: No discussion notes

 

Close Window