New research published by an international team, including scientists from the LCN and UCL, is helping to understand how animal cells divide, migrate and develop.
In collaboration with groups from Canada and France, the researchers looked at the mechanisms behind the emergence of the cell cortex, a thin polymeric network which largely dictates the shape and mechanics of cells, and which plays a fundamental role in cell division, migration, and tissue morphogenesis. The cortex consists of actin filaments cross-linked by actin-binding proteins, on which myosin motor proteins exert mechanical force. Contraction of the cortex plays a crucial role in the migration of metastatic cancer cells and during division, mis-regulation of the cortex can lead to mis-segregation of genetic material.
Despite the importance of the cortex, our knowledge of it is poor: thus far we do not know the answer to key questions such as which proteins nucleate new cortical actin filaments. So, using a combination of biochemical and biophysical assays, the team of researchers set out to investigate the molecular mechanisms that give rise to the filaments that form the actin cortex.
Their research, published in the leading journal Current Biology, shows that two proteins are responsible for nucleating the majority of the actin filaments within the cortex. These two proteins possess radically different assembly kinetics with one several folds order of magnititude faster than the other. Importantly, these biochemical differences also reflected differences in the filament network topologies generated at the microscopic level. One nucleator generated arrays of long linear filaments, while the other formed a dendritic network of short filaments.
According to Dr Guillaume Charras, senior author of this research, this study “is the first step towards an understanding of the mechanics of cells from polymer physics theories”. Based on this data, the team proposes that cells may be able to exploit the difference in growth kinetics and mechanics of the filament networks generated by each nucleator, to rapidly alter their mechanical properties and shape.
Full details on this publication can be found in Current Biology:
Figure: (I) M2 cells stably expressing GFP-actin treated with CK666. 100m M CK666 was added at time point 0:00. Time is in mins. Intensity scales are kept constant between images. Scale bar represents 3mm.
(J) Immunoblot of M2 cells stably transfected with NS or mDia1 shRNA 1 probed with anti-mDia1 and anti-GAPDH.