The Shear Stress of Host Cell Invasion: Exploring the Role of Biomolecular Complexes

Biological fluids, such as blood and mucosal secretions, continuously flow within the human body and form prominent barriers to pathogen colonization and invasion of host cells [1, 2]. Consequently, pathogens have evolved sophisticated molecular strategies to overcome the mechanical shear forces associated with resisting the flow of biological fluids; in particular, membrane anchored biomolecular complexes enable controlled deceleration, tight adhesion and, in the case of intracellular pathogens, penetration through the host cell membrane (Fig. 1A) [3-7]. The architecture of these biomolecular complexes have been the subject of numerous structural and biophysical investigations, which have yielded high resolution molecular blueprints of the host pathogen interface. However, our understanding of precisely how these biomolecular complexes function is somewhat limited by the technical challenges associated with measuring or modelling the effects of shear flow and related forces on protein complexes in the context of biological membranes [8]; recent studies have revealed the development and application of advanced technologies, such as optical tweezers, for studying the roles that mechanical forces play during pathogen attachment, but the stresses associated with subsequent membrane penetration events remain elusive [3, 7, 9]. To highlight the potential for correlating structural and biophysical data with the extent of dynamic shear stress experienced during diverse host cell invasion processes, we review here several structurally characterized invasion complexes from protozoan, bacterial, and viral pathogens.