Loops versus lines and the compression stiffening of cells.

Both animal and plant tissue exhibit a nonlinear rheological phenomenon known as compression stiffening, or an increase in moduli with increasing uniaxial compressive strain. Does such a phenomenon exist in single cells, which are the building blocks of tissues? One expects an individual cell to compression soften since the semiflexible biopolymer-based cytoskeletal network maintains the mechanical integrity of the cell and in vitro semiflexible biopolymer networks typically compression soften. To the contrary, we find that mouse embryonic fibroblasts (mEFs) compression stiffen under uniaxial compression via atomic force microscopy studies. To understand this finding, we uncover several potential mechanisms for compression stiffening. First, we study a single semiflexible polymer loop modeling the actomyosin cortex enclosing a viscous medium modeled as an incompressible fluid. Second, we study a two-dimensional semiflexible polymer/fiber network interspersed with area-conserving loops, which are a proxy for vesicles and fluid-based organelles. Third, we study two-dimensional fiber networks with angular-constraining crosslinks, i.e. semiflexible loops on the mesh scale. In the latter two cases, the loops act as geometric constraints on the fiber network to help stiffen it via increased angular interactions. We find that the single semiflexible polymer loop model agrees well with the experimental cell compression stiffening finding until approximately 35% compressive strain after which bulk fiber network effects may contribute. We also find for the fiber network with area-conserving loops model that the stress-strain curves are sensitive to the packing fraction and size distribution of the area-conserving loops, thereby creating a mechanical fingerprint across different cell types. Finally, we make comparisons between this model and experiments on fibrin networks interlaced with beads as well as discuss implications for single cell compression stiffening at the tissue scale.

Dynamics of certain Euler-Bernoulli rods and rings from a minimal coupling quantum isomorphism.

In some parameter and solution regimes, a minimally coupled nonrelativistic quantum particle in one dimension is isomorphic to a much heavier, vibrating, very thin Euler-Bernoulli rod in three dimensions with ratio of bending modulus to linear density (ℏ/2m)^{2}. For m=m_{e}, this quantity is comparable to that of a microtubule. Axial forces and torques applied to the rod play the role of scalar and vector potentials, respectively, and rod inextensibility plays the role of normalization. We show how an uncertainty principle ΔxΔp_{x}≳ℏ governs transverse deformations propagating down the inextensible, force and torque-free rod, and how orbital angular momentum quantized in units of ℏ or ℏ/2 (depending on calculation method) emerges when the force and torque-free inextensible rod is formed into a ring. For torqued rings with large wave numbers, a "twist quantum" appears that is somewhat analogous to the magnetic flux quantum. These and other results are obtained from a purely classical treatment of the rod, i.e., without quantizing any classical fields.

Compression stiffening in biological tissues: On the possibility of classic elasticity origins.

Compression stiffening, or an increase in shear modulus with increasing compressive strain, has been observed in recent rheometry experiments on brain, liver, and fat tissues. Here we extend the known types of biomaterials exhibiting this phenomenon to include agarose gel and fruit flesh. The data reveal a linear relationship between shear storage modulus and uniaxial prestress, even up to 40% strain in some cases. We focus on this less-familiar linear relationship to show that two different results from classic elasticity theory can account for the phenomenon of linear compression stiffening. One result is due to Barron and Klein, extended here to the relevant geometry and prestresses; the other is due to Birch. For incompressible materials, there are no adjustable parameters in either theory. Which one applies to a given situation is a matter of reference state, suggesting that the reference state is determined by the tendency of the material to develop, or not develop, axial stress (in excess of the applied prestress) when subjected to torsion at constant axial strain. Our experiments and analysis also strengthen the notion that seemingly distinct animal and plant tissues can have mechanically similar behavior at the quantitative level under certain conditions.

Buckling without Bending: A New Paradigm in Morphogenesis.

A curious feature of organ and organoid morphogenesis is that in certain cases, spatial oscillations in the thickness of the growing "film" are out of phase with the deformation of the slower-growing "substrate," while in other cases, the oscillations are in phase. The former cannot be explained by elastic bilayer instability, and contradict the notion that there is a universal mechanism by which brains, intestines, teeth, and other organs develop surface wrinkles and folds. Inspired by the microstructure of the embryonic cerebellum, we develop a new model of 2D morphogenesis in which system-spanning elastic fibers endow the organ with a preferred radius, while a separate fiber network resides in the otherwise fluidlike film at the outer edge of the organ and resists thickness gradients thereof. The tendency of the film to uniformly thicken or thin is described via a "growth potential." Several features of cerebellum, +blebbistatin organoid, and retinal fovea morphogenesis, including out-of-phase behavior and a film thickness amplitude that is comparable to the radius amplitude, are readily explained by our simple analytical model, as may be an observed scale invariance in the number of folds in the cerebellum. We also study a nonlinear variant of the model, propose further biological and bioinspired applications, and address how our model is and is not unique to the developing nervous system.