Nanoscape, a data-driven 3D real-time interactive virtual cell environment.

Our understanding of cellular and structural biology has reached unprecedented levels of detail, and computer visualisation techniques can be used to create three-dimensional (3D) representations of cells and their environment that are useful in both teaching and research. However, extracting and integrating the relevant scientific data, and then presenting them in an effective way, can pose substantial computational and aesthetic challenges. Here we report how computer artists, experts in computer graphics and cell biologists have collaborated to produce a tool called Nanoscape that allows users to explore and interact with 3D representations of cells and their environment that are both scientifically accurate and visually appealing.

Analogies in 3D molecular visualisations: development of a cell biology animation 'How cells move - a new interpretation of old data'.

Cell biology and imaging technology have vastly improved over the past decades, enabling scientists to dissect the inner workings of a cell. In addition to technical limits on spatial and temporal resolution, which obscure the picture at the molecular level, the sheer density and complexity of information impede clear understanding. 3D molecular visualisation has therefore blossomed as a way to translate molecular data in a more tangible form.

A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.

The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo.

ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer death; identifying PDAC enablers may reveal potential therapeutic targets. Expression of the actomyosin regulatory ROCK1 and ROCK2 kinases increased with tumor progression in human and mouse pancreatic tumors, while elevated ROCK1/ROCK2 expression in human patients, or conditional ROCK2 activation in a Kras/p53 mouse PDAC model, was associated with reduced survival. Conditional ROCK1 or ROCK2 activation promoted invasive growth of mouse PDAC cells into three-dimensional collagen matrices by increasing matrix remodeling activities.

Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue.

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology.

The Rac-FRET mouse reveals tight spatiotemporal control of Rac activity in primary cells and tissues.

The small G protein family Rac has numerous regulators that integrate extracellular signals into tight spatiotemporal maps of its activity to promote specific cell morphologies and responses. Here, we have generated a mouse strain, Rac-FRET, which ubiquitously expresses the Raichu-Rac biosensor. It enables FRET imaging and quantification of Rac activity in live tissues and primary cells without affecting cell properties and responses.

Microtubule remodelling is required for the front-rear polarity switch during contact inhibition of locomotion.

When migrating mesenchymal cells collide, they exhibit a 'contact inhibition of locomotion' response that results in reversal of their front-rear polarity by extension of a new leading edge, which enables their migration away from the opposing contacted cell. The critical cytoskeletal rearrangements underpinning these mutual repulsion events are currently unknown. We found that during fibroblast cell-cell collisions, microtubules at the region of contact increase their frequency of catastrophe, their rates of shrinkage and growth, and concomitantly, a new microtubule array is established at a new leading edge.

Competition amongst Eph receptors regulates contact inhibition of locomotion and invasiveness in prostate cancer cells.

Metastatic cancer cells typically fail to halt migration on contact with non-cancer cells. This invasiveness is in contrast to normal mesenchymal cells that retract on contact with another cell. Why cancer cells are defective in contact inhibition of locomotion is not understood.