GENERAL IDEA

Here we explore some of the pioneering single-molecule experiments that have increased our understanding of the processes that essentially involve foreign molecules external to cells either binding to the cell surface or being internalized by cells. Such molecules interact directly with the semipermeable membrane of the cell, making it an exceptionally lively and dynamic environment.

Introduction

Highly efficient mechanisms exist that allow foreign molecules to bind to cell surfaces, ultimately evoking some form of signal response, and allow a variety of external molecules over a broad range of size, chemistry and charge to enter cells. At one level these mechanisms include processes involving receptor molecules embedded in the outer membrane of cells that bind to ligand molecules. Many of the stages of this detection and signal transduction process have canonical features, sometimes involving adapter molecules binding to the original ligand, as well as specific binding events and changes in molecular conformation which can often be transmitted over relatively long length scales of several nanometres spanning one or sometimes more lipid bilayer membranes and sometimes involving cooperative effects from other receptor molecules. Non-native particles which are internalized by cells range in size from single molecules to much larger heterogenous macromolecular complexes such as viruses. In this chapter we will encounter first-hand examples of how these processes have been investigated using single-molecule biophysics. These investigations reveal highly complex behaviours, indicating that the world outside the cell is just as important as the world on the inside.