Poster Presentation 2014 International Biophysics Congress

Single molecule view of actin - tropomyosin filament dynamics (#658)

Tom L. Sobey 1 , Peyman Obeidy 1 , Philip Nicovich 2 , Miro Janco 1 , Adelle Coster 3 , Peter Gunning 4 , Till Böcking 1
  1. Molecular Machines Group, Centre for Vascular Research, UNSW, Sydney, VIC, Australia
  2. Biomedical Imaging Facility, UNSW, Sydney, VIC, Australia
  3. School of Mathematics and Statistics, UNSW, Sydney, Australia
  4. Oncology Research Unity, School of Medical Sciences, UNSW, Sydney, Australia

Actin is one of the most prominent proteins in our bodies. It plays vitally important roles both in muscle and in the cytoskeleton of cells, where filaments are involved in most cellular processes including determination of cell shape, cell migration, cell division, membrane function, and intracellular transport. It's primary binding partner is tropomyosin, which provides crucial stabilisation and regulatory functionality. Here we investigate at the single molecule level how tropomyosin and actin interact with each other. This answers fundamental questions about the molecular mechanisms, dynamics and kinetics which provide key insights into the differing roles of tropomyosin isoforms. There are over 22 human isoforms, and many are found in close proximity on nearby actin filaments within the cell. One key question is how different isoforms sort to different actin filaments within such a neighbourhood: are there intrinsic mechanisms - such as the first tropomyosin molecule to bind changing the filament structure so that only the same isoform can bind - or are there external factors such as binding cofactors necessary? We make use of TIRF microscopy and microfluidics to provide key insights into answering these questions. A long held view in the field has been that the actin filaments first polymerise, and that tropomyosin then binds to the naked actin filament. We have shown however that tropomyosin has a much lower dissociation constant when copolymerised together with the actin filament, rather than binding to the filament after it has formed. This indicates that former has enhanced binding and suggests that this occurs rather than the ‘naked actin filament’ theory.