Effects of macromolecular crowding on intracellular diffusion from a single particle perspective

Compared to biochemical reactions taking place in relatively well-defined aqueous solutions in vitro, the corresponding reactions happening in vivo occur in extremely complex environments containing only 60–70% water by volume, with the remainder consisting of an undefined array of bio-molecules. In a biological setting, such extremely complex and volume-occupied solution environments are termed ‘crowded’. Through a range of intermolecular forces and pseudo-forces, this complex background environment may cause biochemical reactions to behave differently to their in vitro counterparts. In this review, we seek to highlight how the complex background environment of the cell can affect the diffusion of substances within it. Engaging the subject from the perspective of a single particle’s motion, we place the focus of our review on two areas: (1) experimental procedures for conducting single particle tracking experiments within cells along with methods for extracting information from these experiments; (2) theoretical factors affecting the translational diffusion of single molecules within crowded two-dimensional membrane and three-dimensional solution environments. We conclude by discussing a number of recent publications relating to intracellular diffusion in light of the reviewed material

Tumour-stromal interactions:phenotypic and genetic alterations in mammary stroma: implications for tumour progression

In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in the present review extend the repertoire of matrix signalling mechanisms, (1) introducing the concept of 'matrikines', these defined as proteinase-generated fragments of matrix macromolecules that display cryptic bioactivities not manifested by the native, full-length form of the molecule, and (2) indicating that a previously identified motogenic factor (migration stimulating factor [MSF]) produced by foetal and cancer patient fibroblasts is a genetically generated truncated isoform of fibronectin, which displays bioactivities cryptic in all previously identified fibronectin isoforms. These observations are discussed in the context of the contribution of a 'foetal-like' stroma to the progression of breast cancer

CFTR expression and activity from the human CFTR locus in BAC vectors, with regulatory regions, isolated by a single-step procedure

In pres