Biological horizons in molecular microscopy

Abstract

The purpose envisaged in this report is not to provide a comprehensive monography but rather to give a survey, especially for biologists, of the state of the art and of current research trends in molecular microscopy. Following a brief discussion of the obvious discrepancy between instrumental capabilities and the limits of biologically significant information, a definition of the diversifying field is attempted. Four main topics are discussed. First, recent progress in the field of "low noise" specimen supports is reviewed. It is emphasized that a minimum background structure is an important but not the sole criterion for a satisfactory support. It is the ability to adsorb molecules in a predeterminable and orderly fashion which will attract wider attention in the future; positional and orientational order figure as crucial points in the strategem of low dose microscopy. Second, the problem of achieving adequate contrast without the expense of an unfaithful representation of molecular structures is discussed. Contrast is a problem of optimum imaging modes as well as of preparatory techniques. The third topic of discussion is specimen dehydration. Several avenues to circumvent or at least to alleviate dehydration artifacts are outlined. The last chapter focusses on the most fundamental problem in molecular microscopy:radiation damage. A brief synopsis of the physical and physico-chemical processes involved in damaging interactions is given and an attempt is made to tesselate the true picture of radiation damage to lipids and proteins. This might serve as a guidance in assessing the degree of structural fidelity to be expected for a given electron dose. Possibilities to overcome the radiation damage problem are adumbrated.