Figure 1.

A schematic illustrating how small protein probes (such as BZip) tagged with fluorescent particles may interact with different areas of the nucleus. White: laser-illuminated confocal volume inside the nuclear ROI. Black ovals: Different local environment areas. Proteins (red) diffuse across the heterogeneous illuminated area of the nucleus. In area (A) the protein diffuses essentially freely as the area is largely clear. In area (B) the protein is diffusing through a crowded area without specifically interacting with the molecules there (gray) except via Brownian collisions. In area (C) the protein is diffusing while binding nonspecifically to an area of DNA where it has no specific targets (green rectangles), and in area (D) the protein has encountered one of its targets, i.e., a high-affinity DNA site (blue rectangle) to which it binds long enough to slow its diffusion. To see this figure in color, go online.