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Research Departments > Molecular, Cellular and Developmental Neurobiology department > Protein nanomechanics in the nervous system > Research Report

Research Report Personnel Publications Other

Protein nanomechanics in the nervous system

Own lab page: http://carrionvazquez-lab.org

The general interest of our laboratory is to understand the inner workings of proteins. In particular, we are studying the nanomechanical properties of several bio-nanomachines from the nervous system: the proteasome (and its neurotoxic substrate proteins), the cellular adhesion machinery, and the membrane fusion machinery.

1) Nanomechanics of the proteasome and its neurotoxic substrate proteins (huntingtin, β-amyloid, α-synuclein and prions).

1.1. Testing two hypotheses: a) mechanical mechanism for the “unfoldase” of the proteasome, b) the possibility that neurotoxic proteins may have a mechanical stability higher than the traction capacity of the proteasome, which would unable this structure from processing them.

1.2. Direct study of the dynamics of formation of oligomers and aggregates in real time and with nanoscopic resolution.

2) 2) Nanomechanics of the cell adhesion machinery (synaptic and auditory cadherins).

2.1. Testing the hypothesis that suggests that modules from cell adhesion proteins may work as mechanical shock absorbers that would protect bonds between cells.

2.2. Developing an unequivocal system to directly measure intercellular interactions in pairs of single molecules.

2.3. Direct study of the dynamics of formation of cadherin oligomers in real time and with nanoscopic resolution.

3) Nanomechanics of the membrane fusion machinery (SNAREs).
The process of membrane fusion is energetically highly improbably (due to the electrostatic repulsion and dehydration involved). We are interested in measuring the traction forces generated by this complex as well as its mechanical stability. We are developing a strategy to unequivocally measure intermolecular interactions by force spectroscopy.

Most relevant methodology:

The basic methodology we use falls into what could be called “single-molecule biochemistry”. The aim of it is the study of protein function one molecule at a time. This strategy allows the nanoscopic analysis of the dynamics of protein molecules in real time and physiological conditions. Specifically, we use the atomic force microscopy (AFM) in its two modes (single-molecule force spectroscopy and imaging). This technique allows the manipulation, the nanomechanical analysis, and the “mechanical visualization” of individual protein molecules. We complement this technique with genetic engineering, protein engineering, gene replacement and computer simulations.

Our long-term goal is the study of protein nanomechanics in the interior of living cells and organisms. For this purpose we are developing a molecular force sensor that would allow measuring mechanical forces in vivo.

 

 



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