The role of Vimentin in Regulating Cell Invasive Migration in Dense Cultures of Breast Carcinoma Cells.

Cell migration and mechanics are tightly regulated by the integrated activities of the various cytoskeletal networks. In cancer cells, cytoskeletal modulations have been implicated in the loss of tissue integrity and acquisition of an invasive phenotype. In epithelial cancers, for example, increased expression of the cytoskeletal filament protein vimentin correlates with metastatic potential.

Phosphorylation-Induced Mechanical Regulation of Intrinsically Disordered Neurofilament Proteins.

The biological function of protein assemblies has been conventionally equated with a unique three-dimensional protein structure and protein-specific interactions. However, in the past 20 years it has been found that some assemblies contain long flexible regions that adopt multiple structural conformations. These include neurofilament proteins that constitute the stress-responsive supportive network of neurons.

Neurofilaments Function as Shock Absorbers: Compression Response Arising from Disordered Proteins.

What can cells gain by using disordered, rather than folded, proteins in the architecture of their skeleton? Disordered proteins take multiple coexisting conformations, and often contain segments which act as random-walk-shaped polymers. Using x-ray scattering we measure the compression response of disordered protein hydrogels, which are the main stress-responsive component of neuron cells. We find that at high compression their mechanics are dominated by gaslike steric and ionic repulsions.

Order and disorder in intermediate filament proteins.

Intermediate filaments (IFs), important components of the cytoskeleton, provide a versatile, tunable network of self-assembled proteins. IF proteins contain three distinct domains: an α-helical structured rod domain, flanked by intrinsically disordered head and tail domains. Recent studies demonstrated the functional importance of the disordered domains, which differ in length and amino-acid sequence among the 70 different human IF genes.

Probing the interactions of intrinsically disordered proteins using nanoparticle tags.

The structural plasticity of intrinsically disordered proteins serves as a rich area for scientific inquiry. Such proteins lack a fix three-dimensional structure but can interact with multiple partners through numerous weak bonds. Nevertheless, this intrinsic plasticity possesses a challenging hurdle in their characterization.

Neurofilament assembly and function during neuronal development.

Studies on the assembly of neuronal intermediate filaments (IFs) date back to the early work of Alzheimer. Developing neurons express a series of IF proteins, sequentially, at distinct stages of mammalian cell differentiation. This correlates with altered morphologies during the neuronal development, including axon outgrowth, guidance and conductivity.

Met kinetic signature derived from the response to HGF/SF in a cellular model predicts breast cancer patient survival.

To determine the signaling pathways leading from Met activation to metastasis and poor prognosis, we measured the kinetic gene alterations in breast cancer cell lines in response to HGF/SF. Using a network inference tool we analyzed the putative protein-protein interaction pathways leading from Met to these genes and studied their specificity to Met and prognostic potential. We identified a Met kinetic signature consisting of 131 genes.