Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

Abstract

Abstract-Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano-and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

Defining the role of syndecan-4 in mechanotransduction using surface-modification approaches

“…Syndecan-4 molecules have been shown to indirectly attach to primary protein components of the FAC, including paxillin, that is linked to the actin cytoskeleton (16). In addition, studies have already indicated that heparin sulfate-linked proteins could have a role in mechanical signaling (15) and have been implicated in numerous processes from cell signaling to adhesion (18). Furthermore, in tests of mechanotransduction using integrin-based adhesion, syndecans are known to cluster at the FAC, potentially implicating them in this pathway and reinforcing their interrelationship to the process of mechanical activation (19).…”

Micro- and Nanotechnology in Tissue Engineering

“…One of the major motivations for the increasing effort spent on designing and developing nanostructured materials for TE strategies is that natural tissues and the associated extracellular matrices are in fact composed of nanostructured materials [3,69,104] ( Fig. 1.2).…”

Nanoscale imaging and force probing of biomolecular systems using atomic force microscopy: from single molecules to living cells

“…Down to the single-cell level, it is known that the fulfillment of cell functions is based on a complex set of molecular interactions which control signaling pathways to influence ultimate cell fates, including proliferation, differentiation, and apoptosis. 12 These molecular interactions predominate at the nanoscale. 13 Therefore, in principle, in order to thoroughly understand the underlying mechanisms guiding cellular behaviors, directly observing molecular activities taking place at the nanoscale is indispensable.…”