Once upon a (length and) time (scale). . .

Abstract

Truly it has been said, that to a clear eye the smallest fact is a window through which the Infinite may be seen . (T. H. Huxley, The Study of Zoology , 1861) GENERAL IDEA Here we discuss the conceptual foundations of single-molecule biophysics in the context of cellular biology. We provide an overview of existing ensemble average techniques used to study biological processes and consider the importance of single-molecule biology experiments. Introduction Some of the most talented physicists in modern science history have been led ultimately to address challenging questions of biology. This is exemplified in Erwin Schrodinger’s essay ‘What is Life?’ (see Schrodinger, 1944). It starts with the question ‘How can the events in space and time which take place within the spatial boundary of a living organism be accounted for by physics and chemistry?’ In other words, can we address the big questions of the life sciences from the standpoint of the physical sciences. The ~60 years following the publication of this seminal work has seen a vast increase in our understanding of biology at the molecular scale, and the physical sciences have played a key role in resolving many central problems. The biological problems have not been made easier by the absence of a compelling and consistent definition of ‘life’ – writing from the context for a meaning of ‘artificial life’, the American journalist Steven Levy noted 48 examples of definitions of life from eminent scientists, no two of which were the same (Levy, 1993). From a physical perspective, life is a means of trapping free energy (ultimately from the sun or, more rarely, geological thermal vents) into units of increased local order, which in effect locally decrease entropy, while the units maintain their status in situations which are generally far from thermal equilibrium.