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An innovative biomimetic model of the cell cytoskeleton

Cell shape and rigidity are conferred by the cytoskeleton, a polymer network mainly composed of filaments that form a cellular scaffold. To characterise the mechanical properties of the cytoskeleton in relation to its composition, a European study proposes to generate a hybrid network between actin and DNA.
An innovative biomimetic model of the cell cytoskeleton
The capability of cells to actively adapt their structure and mechanical properties is ensured by cytoskeletal protein motors such as myosin II. This is usually triggered by changes in the physical properties of the surrounding tissue, which are sensed by the cell through protein complexes, known as focal adhesions, localised in its cell membrane.

Mechanical properties of the cytoskeleton determine how mechanical forces are sensed by the cell, and propagated through and transmitted to the extracellular matrix. The main scientific objective of the EU-funded 'Biomimetic model of the cell cytoskeleton: Polymer networks cross-linked with DNA strands' (BIOLINK) project is to understand the physics behind the mechanical adaptability of cytoskeletal networks. The key to this is to investigate the interplay between the activity of molecular motors and the mechanical properties of the cytoskeleton, dictated to a large extent by cross-linkers.

To achieve this goal, the plan is to develop a unique model system that consists of actin filaments hybridised to DNA molecules. By varying the length of DNA to cross-link actin, scientists envision being able to control the strength and rigidity of the cytoskeletal biomaterial. Covalent and non-covalent linking of DNA to actin is being tested for the preparation of the network.

Using this experimental assay, scientists will study the dynamic rheological properties and the non-linear viscoelastic response of the actin–DNA network. Direct imaging will also enable a 3D reconstruction of the network structure and the generation of theoretical models.

Furthermore, scientists are interested in correlating motor activity with cross-linker structure for controlling self-organisation of active biopolymer networks. To achieve this, and evaluate the influence of motor activity on network rheology, they will use laser tweezers to perform active and passive microrheology.

BIOLINK findings will increase our understanding of the role that physical interactions may play in the regulation of processes such as tissue morphogenesis. Moreover, the developed cytoskeletal biomimetic is expected to serve as a basis for the creation of cell-inspired materials for materials science purposes, and of tissue-like matrices that could be exploited in tissue engineering.

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