Interaction of Synthetic Polymers with Cell Membranes and Model Membrane Systems I. Differential Scanning Calorimetry

Abstract

Preliminary successes in the development of biologically active synthetic polymers have demonstrated a need for a deeper understanding of the interactions between soluble synthetic polymers and biological molecules or biological surfaces. For example, we have shown that some polymeric derivatives of salicylic acid exhibit antibacterial activity specifically against Gram-negative strains, while the low molecular weight analogues are non-specific. A plausible interpretation of this result is that polymerization produces an antibacterial ,agent which is highly hydrophobic, and which therefore interacts more strongly with the lipid-rich wall of the Gram-negative cell than with the lipid-poor wall of the Gram-positive cell. Unfortunately, there exists in the literature very little, if any, information which one can use to assess this idea; virtually nothing is known about the nature and magnitude of the interactions of soluble synthetic polymers with cell surfaces. The situation is quite different with natural polymers: intense study of natural macromolecules such as insulin, bacterial toxins and various plant and animal lectins has in some cases yielded quite thorough understanding of their cell-surface interactions. The objective of our work in this area is to bring the understanding of synthetic polymer-membrane interactions to a comparable level. Using prior work on natural polymers as a guide, we have undertaken experiments of three kinds: i) differential scanning calorimetry (DSC), which allows one to observe structural changes in the membrane which result from interaction with a polymeric solute, ii) cell agglutination (aggregation) measurements, which allow a rapid assessment of the magnitude of interaction and which can identify specific binding sites, and iii) direct binding (adsorption) measurements using radiolabelled synthetic polymers. In all of these experiments, we are using human red blood cells (erythrocytes), or red cell "ghosts" prepared by hypotonic hemolysis; that is, we have selected the human red cell membrane as a model natural membrane. This selection was based on three factors: i) the erythrocyte membrane is readily isolated, ii) calorimetry has been used previously to investigate the interaction of small molecules with erythrocyte and iii) systemic use of polymeric drugs can produce undesirable side effects which may be related to interaction with the red blood cell. The present paper demonstrates the use of high-sensitivity differential scanning calorimetry in the study of the interaction of synthetic polymers with cell surfaces.

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