Model of Tumor Growth and Response to Radiation

Abstract

Biological membranes have developed to separate different compartments of organisms and cells. There is a large number of rather different functions which membranes have to fulfil: (1) they control the material and energy fluxes of metabolic processes, (2) they provide a wrapping protecting the compartments from chemical and physical attacks of the environment, (3) they provide interfaces at which specific biochemical machineries can operate (e.g., membrane bound enzymes), (4) they are equipped for signal transduction, (5) they possess the necessary stability and flexibility to allow cell division, and endo- and exocytosis as well as migration, (6) they present anchoring structures that enable cell-to-cell and cell-to-matrix physical interactions and intercellular communication. These are certainly not all functions of membranes as new functionalities are continuously reported. Since the biological membranes separate essentially aqueous solutions, such separating borders—if they should possess a reasonable stability and also flexibility combined with selective permeability—have to be built up of hydrophobic molecules exposing to both sides a similar interface. It was one of the most crucial and most lucky circumstances for the development and existence of life that certain amphiphilic molecules are able to assemble in bilayer structures (membranes), which—on one side—possess a rather high physical and chemical stability, and—on the other side—are able to incorporate foreign molecules for modifying both the physical properties as well as the permeability of the membranes for defined chemical species. The importance of the chemical function of membranes and all its constituents, e.g., ion channels, pore peptides, transport peptides, etc., is generally accepted. The fluid-mosaic model proposed by Singer and Nicolson [1] is still the basis to understand the biological, chemical, and physical properties of biological membranes. The importance of the purely mechanical properties of membranes came much later into the focus of research. The reasons are probably the dominance of biochemical thinking and biochemical models among biologists and medical researchers, as well as a certain lack of appropriate methods to probe mechanical properties of membranes. The last decades have changed that situation due to the development of techniques like the Atomic Force Microscopy, Fluorescence Microscopy, Micropipette Aspiration, Raman Microspectroscopy, advanced Calorimetry, etc. This chapter is aimed at elucidating how the properties of membranes can be investigated by studying the interaction of vesicles with a very hydrophobic surface, i.e., with the surface of a mercury electrode. This interaction is unique as it results in a complete disintegration of the bilayer membrane of the vesicles and the formation of an island of adsorbed lipid molecules, i.e., a monolayer island. This process can be followed by current-time measurements (chronoamperometry), which allow studying the complete disintegration process in all its details: the different steps of that disintegration can be resolved on the time scale and the activation parameters can be determined. Most interestingly, the kinetics of vesicle disintegration on mercury share important features with the process of vesicle fusion and, thus, sheds light also on mechanisms of endocytosis and exocytosis. Most importantly, not only artificial vesicles (liposomes) can be studied with this approach, but also reconstituted plasma membrane vesicles and even intact mitochondria. Hence, one can expect that the method may provide in future studies also information on the membrane properties of various other vesicles, including exosomes, and may allow investigating various aspects of drug action in relation to membrane properties (transmembrane transport, tissue targeting, bioavailability, etc.), and also the impact of pathophysiological conditions (e.g., oxidative modification) on membrane properties, on a hitherto not or only hardly accessible level.