Nonlinear mechanics of hybrid polymer networks that mimic the complex mechanical environment of cells

Abstract

The mechanical properties of cells and the extracellular environment they reside in are governed by a complex interplay of biopolymers. These biopolymers, which possess a wide range of stiffnesses, self-assemble into fibrous composite networks such as the cytoskeleton and extracellular matrix. They interact with each other both physically and chemically to create a highly responsive and adaptive mechanical environment that stiffens when stressed or strained. Here we show that hybrid networks of a synthetic mimic of biological networks and either stiff, flexible and semi-flexible components, even very low concentrations of these added components, strongly affect the network stiffness and/or its strain-responsive character. The stiffness (persistence length) of the second network, its concentration and the interaction between the components are all parameters that can be used to tune the mechanics of the hybrids. The equivalence of these hybrids with biological composites is striking.

Tailored Combinatorial Microcompartments through the Self‐Organization of Microobjects: Assembly, Characterization, and Cell Studies

“…[4] Among the fabrication methods,classic photolithographic approaches,b ut also hot embossing, direct write approaches, and micromolding in capillaries (MIMIC), have been used to fabricate 3D microwells. [5] Thes tructures implemented for example in the work of the de Boer group [3,6] represent one of the many determinants of the interactions of cells with their surroundings.A dditionally,b iochemical cues (peptide sequences), their density, [7] nanoscale arrangement, and spacing [8] as well as the mechanical properties [9] of the extracellular matrix (ECM) or ECM mimics must be considered. It is clear that current micro-and nanofabrication approaches,w hich are essentially projection-based approaches,i nherently possess their limitations in the fabrication of complex asymmetric microcompartments,i nw hich all of these parameters are varied independently.…”

Maximally stiffening composites require maximally coupled rather than maximally entangled polymer species

“…Proteins, DNA, and microspheres: Monomeric rabbit skeletal muscle actin (Cytoskeleton, AKL99) was stored at −80 o C in G-buffer [2 mM Tris pH 8.0, 0.2 mM ATP, 0.5 mM DTT, 0.1 mM CaCl 2 ]. Linear double-stranded DNA of lengths 11 kbp (3.67 µm), 115 kbp (39 µm) and 289 kbp (96 µm) were prepared via replication of supercoiled plasmids (11 kbp) and bacterial artificial chromosomes (BACs, 115, 289 kbp) in Escherichia coli, followed by extraction, purification and enzymatic linearization as described previously [9]. BamHI and Mlu1 (New England Biolabs) were used to linearize the plasmid and BACs respectively.…”

“…However, the shortest DNA is in a concentration regime in between those for which Eqs. (8) and (9) are valid, with c * 0.13 mg/ml (or c/c * 1 − 6), so we expect actin bundling to depend on R g as well as c DN A . Additionally, in this less entangled regime we expect the g A,A (r) curves to depend on DNA's R g and therefore L DN A , as observed in Fig.…”

“…Composites or polymer mixtures have been shown to display emergent mechanical and rheological properties that are not a simple superposition of the corresponding single-component systems but strongly depend on, e.g., entropic or enthalpic interaction between the species [3,4], their softness [5], or topology [6]. In fact, these behaviours are often completely unexpected given the starting materials [7][8][9] and include nonlinear stress-stiffening [10][11][12], asymmetric caging in soft colloidal glasses [5], negative normal stress [13,14], and strength with simultaneous lack of brittleness [2]. While we have only recently begun to appreciate the physics underlying the emergent material properties of polymer composites, nature has already exploited their design principles to allow for multifunctional mechanics and dynamic processes in the cell nucleus [15][16][17], cytoskeleton [9,18,19] and extracellular matrix [9,20].…”

“…In fact, these behaviours are often completely unexpected given the starting materials [7][8][9] and include nonlinear stress-stiffening [10][11][12], asymmetric caging in soft colloidal glasses [5], negative normal stress [13,14], and strength with simultaneous lack of brittleness [2]. While we have only recently begun to appreciate the physics underlying the emergent material properties of polymer composites, nature has already exploited their design principles to allow for multifunctional mechanics and dynamic processes in the cell nucleus [15][16][17], cytoskeleton [9,18,19] and extracellular matrix [9,20]. As such, while understanding the design principles of polymer composites is important for synthetic applications [21,22], it also directly informs complex biological networks and paves the way for new biomimetic materials [2].…”