From isolated structures to continuous networks: A categorization of cytoskeleton‐based motile engineered biological microstructures

Abstract

As technology at the small scale is advancing, motile engineered microstructures are becoming useful in drug delivery, biomedicine, and lab-on-a-chip devices. However, traditional engineering methods and materials can be inefficient or functionally inadequate for small-scale applications. Increasingly, researchers are turning to the biology of the cytoskeleton, including microtubules, actin filaments, kinesins, dyneins, myosins, and associated proteins, for both inspiration and solutions. They are engineering structures with components that range from being entirely biological to being entirely synthetic mimics of biology and on scales that range from isotropic continuous networks to single isolated structures. Motile biological microstructures trace their origins from the development of assays used to study the cytoskeleton to the array of structures currently available today. We define 12 types of motile biological microstructures, based on four categories: entirely biological, modular, hybrid, and synthetic, and three scales: networks, clusters, and isolated structures. We highlight some key examples, the unique functionalities, and the potential applications of each microstructure type, and we summarize the quantitative models that enable engineering them. By categorizing the diversity of motile biological microstructures in this way, we aim to establish a framework to classify these structures, define the gaps in current research, and spur ideas to fill those gaps. active matter, biomimicry, biomolecular motor protein, cytoskeletal networks, microscale devicesThe challenges of biomedical research and development often lie at the interface between the medical intervention and the biological material. The relevant scale of this interface is on the order of nanometers (molecular scale) or smaller for drug developers, and the relevant scale of this interface is on the order of millimeters (tissue scale) or larger for biomedical device designers. However, there is an emerging class of biomedical solutions with scale on the order of micrometers (cellular scale).

Wrinkling Instability in 3D Active Nematics

“… 3 − 10 Several experimental and theoretical model systems have been developed to study networks of cytoskeletal filaments and motor proteins fueled by ATP. 11 − 13 A remarkable example is the emergent behavior in 2D observed in mixtures of microtubules and kinesin motors arranged in bundles by a depletion agent pioneered by Sanchez et al 12 Internally generated spatiotemporally chaotic flows at the millimeter scale were observed that persisted as long as ATP was available. The 2D networks exhibit a steady state with permanent flow at large scales, while the dynamics is driven by the buckling and elongation of the microtubule bundles due to the activity of the motors on the nanometer scale.…”

Learning from Embryo Development to Engineer Self‐organizing Materials

“…The first author to suggest that pattern formation in living systems may have a chemical basis was Alan Turing in 1952 [130,129] in the landmark paper The chemical basis of morphogenesis. 1 Turing discovered that a mixture of chemical species that react and diffuse can, in some cases, generate an inhomogeneous concentration pattern from an initially homogeneous state and thus break the symmetry spontaneously. Such a mixture is called a reaction-diffusion (RD) system and the mechanism of symmetry-breaking receives the name of spatial instability.…”

“…Such a mixture is called a reaction-diffusion (RD) system and the mechanism of symmetry-breaking receives the name of spatial instability. This instability happens only under the following necessary condi- 1 For a historical perspective see ref. 3. tions:…”

“…The cytoskeleton plays a central role in the organization of eukaryote cells. It is a dynamic structure and a prototypical dissipative material that has been investigated both for its fundamental importance in biology [20,10] and as a building block of artificial systems [94,1]. Two of the main constituents of the cytoskeleton are actin filaments and microtubules and their associated molecular motors.…”

“…These two filamentous systems have very different physico-chemical properties associated with distinct cellular functions. Actin filaments are polymers of actin with a double-helical structure that make them relatively flexible (with a persistence length l p ≈ 20 µm [11,1]). Microtubules are polymers of tubulin with a tubular structure that make them particularly rigid (l p ≈ 1 − 5 mm) but allow them to buckle when compressed [116,1].…”