Multiscale architecture: Mechanics of composite cytoskeletal networks

Abstract

Different types of biological cells respond differently to mechanical stresses, and these responses are mainly governed by the cytoskeleton. The main components of this biopolymer network are actin filaments, microtubules, and intermediate filaments, whose mechanical and dynamic properties are highly distinct, thus opening up a large mechanical parameter space. Aside from experiments on whole, living cells, “bottom-up” approaches, utilizing purified, reconstituted protein systems, tremendously help to shed light on the complex mechanics of cytoskeletal networks. Such experiments are relevant in at least three aspects: (i) from a fundamental point of view, cytoskeletal networks provide a perfect model system for polymer physics; (ii) in materials science and “synthetic cell” approaches, one goal is to fully understand properties of cellular materials and reconstitute them in synthetic systems; (iii) many diseases are associated with cell mechanics, so a thorough understanding of the underlying phenomena may help solving pressing biomedical questions. In this review, we discuss the work on networks consisting of one, two, or all three types of filaments, entangled or cross-linked, and consider active elements such as molecular motors and dynamically growing filaments. Interestingly, tuning the interactions among the different filament types results in emergent network properties. We discuss current experimental challenges, such as the comparability of different studies, and recent methodological advances concerning the quantification of attractive forces between filaments and their influence on network mechanics.

Cell-Sized Confinements Alter Molecular Diffusion in Concentrated Polymer Solutions Due to Length-Dependent Wetting of Polymers

“…The cytoplasm of living cells typically contains numerous (macro)­molecular components at high concentrations. , These components cover a wide size spectrum, ranging from a few nanometers in single proteins to several micrometers in cytoskeletal filaments. The positioning of these components within the cell is strongly tied to their biological functions; e.g., the long-lived cytoskeleton formed by intermediate filaments beneath the cell membrane exhibits strain stiffening in response to an external load, thereby protecting cells from harmful deformations . The identity and concentration of the (macro) molecular components can be analyzed from the fluorescence labeling of target molecules and measurements of local physical properties, such as the refractive index (RI), polarization, and absorption efficiency of light. , …”

“…The positioning of these components within the cell is strongly tied to their biological functions; e.g., the long-lived cytoskeleton formed by intermediate filaments beneath the cell membrane exhibits strain stiffening in response to an external load, thereby protecting cells from harmful deformations. 3 The identity and concentration of the (macro) molecular components can be analyzed from the fluorescence labeling of target molecules 4 and measurements of local physical properties, such as the refractive index (RI), 5 polarization, 6 and absorption efficiency of light. 7,8 Recently, the dynamic formation of biomolecular condensates through liquid−liquid phase separation (LLPS) has attracted attention as a mechanism to regulate the dynamic positioning of molecules.…”

Cell Shape and Forces in Elastic and Structured Environments: From Single Cells to Organoids

“…[ 28 ] While each filament system is well‐investigated by itself, the interplay between them is the topic of much on‐going research. [ 29 ] Very importantly, cell mechanics are also strongly determined by the mechanics of the nucleus, which is typically ten times stiffer than the cytoplasm and tightly integrated with the cytoskeleton through the LINC‐complexes. [ 30 ] It has been argued earlier that cells have to use their cytoskeleton to sense and calibrate mechanical cues from their environment, [ 31 ] and today the nucleus should be added as an additional measurement devise.…”

Modelling cell shape in 3D structured environments: A quantitative comparison with experiments

“…Other internal structures relevant to cell shape include the nucleus, which is anchored in the cytoskeleton, actin stress fibers, which are actomyosin filament bundles that form dynamically in response to the mechanical environment, microtubules, stiff hollow structures that provide intracellular coordination and stability, and intermediate filaments, which contribute to cell integrity and resilience against external stress, mainly in epithelial cells [4][5][6]. Although our understanding of each system is increasing, the interplay between the three filament systems is crucial for cell mechanics and their resulting cell shape is difficult to predict due to the complexity of the system [7].…”