F. C. MacKintosh

Nonlinear elasticity in biological gels

The mechanical properties of soft biological tissues are essential to their physiological function and cannot easily be duplicated by synthetic materials. Unlike simple polymer gels, many biological materials—including blood vessels, mesentery tissue, lung parenchyma, cornea and blood clots—stiffen as they are strained, thereby preventing large deformations that could threaten tissue integrity. The molecular structures and design principles responsible for this nonlinear elasticity are unknown. Here we report a molecular theory that accounts for strain-stiffening in a range of molecularly distinct gels formed from cytoskeletal and extracellular proteins and that reveals universal stress–strain relations at low to intermediate strains. The input to this theory is the force–extension curve for individual semi-flexible filaments and the assumptions that biological networks composed of these filaments are homogeneous, isotropic, and that they strain uniformly. This theory shows that systems of filamentous proteins arranged in an open crosslinked mesh invariably stiffen at low strains without requiring a specific architecture or multiple elements with different intrinsic stiffness.

Elasticity of semiflexible biopolymer networks.

We develop a model for cross-linked gels and sterically entangled solutions of semiflexible biopolymers such as F-actin. Such networks play a crucial structural role in the cytoskeleton of cells. We show that the rheologic properties of these networks can result from nonclassical rubber elasticity. This model can explain a number of elastic properties of such networks in vitro, including the concentration dependence of the storage modulus and yield strain.

Tuning bilayer twist using chiral counterions

From seashells to DNA, chirality is expressed at every level of biological structures. In self-assembled structures it may emerge cooperatively from chirality at the molecular scale. Amphiphilic molecules, for example, can form a variety of aggregates and mesophases that express the chirality of their constituent molecules at a supramolecular scale of micrometres (refs 1–3). Quantitative prediction of the large-scale chirality based on that at themolecular scale remains a largely unsolved problem. Furthermore, experimental control over the expression of chirality at the supramolecular level is difficult to achieve: mixing of different enantiomers usually results in phase separation. Here we present an experimental and theoretical description of a system in which chirality can be varied continuously and controllably (‘tuned’) in micrometre-scale structures. We observe the formation of twisted ribbons consisting of bilayers of gemini surfactants (two surfactant molecules covalently linked at their charged head groups). We find that the degree of twist and the pitch of the ribbons can be tuned by the introduction of opposite-handed chiral counterions in various proportions. This degree of control might be of practical value; for example, in the use of thehelical structures as templates for helical crystallization of macromolecules,.

Microtubules can bear enhanced compressive loads in living cells because of lateral reinforcement

Cytoskeletal microtubules have been proposed to influence cell shape and mechanics based on their ability to resist large-scale compressive forces exerted by the surrounding contractile cytoskeleton. Consistent with this, cytoplasmic microtubules are often highly curved and appear buckled because of compressive loads. However, the results of in vitro studies suggest that microtubules should buckle at much larger length scales, withstanding only exceedingly small compressive forces. This discrepancy calls into question the structural role of microtubules, and highlights our lack of quantitative knowledge of the magnitude of the forces they experience and can withstand in living cells. We show that intracellular microtubules do bear large-scale compressive loads from a variety of physiological forces, but their buckling wavelength is reduced significantly because of mechanical coupling to the surrounding elastic cytoskeleton. We quantitatively explain this behavior, and show that this coupling dramatically increases the compressive forces that microtubules can sustain, suggesting they can make a more significant structural contribution to the mechanical behavior of the cell than previously thought possible.

Microscopic Viscoelasticity: Shear Moduli of Soft Materials Determined from Thermal Fluctuations

We describe a high-resolution, high-bandwidth technique for determining the local viscoelasticity of soft materials such as polymer gels. Loss and storage shear moduli are determined from the power spectra of thermal fluctuations of embedded micron-sized probe particles, observed with an interferometric microscope. This provides a passive, small-amplitude measurement of rheological properties over a much broader frequency range than previously accessible to microrheology. We study both F-actin biopolymer solutions and polyacrylamide (PAAm) gels, as model semiflexible and flexible systems, respectively. We observe high-frequency

Mixed microtubules steer dynein-driven cargo transport into dendrites.

{\ensuremath{\omega}}^{3/4}

An active biopolymer network controlled by molecular motors

scaling of the shear modulus in F-actin solutions, in contrast to

Distinct regimes of elastic response and deformation modes of cross-linked cytoskeletal and semiflexible polymer networks

{\ensuremath{\omega}}^{1/2}

Deformation of Cross-Linked Semiflexible Polymer Networks

scaling for PAAm.

Modeling semiflexible polymer networks

BACKGROUND To establish and maintain their polarized morphology, neurons employ active transport driven by molecular motors to sort cargo between axons and dendrites. However, the basic traffic rules governing polarized transport on neuronal microtubule arrays are unclear. RESULTS Here we show that the microtubule minus-end-directed motor dynein is required for the polarized targeting of dendrite-specific cargo, such as AMPA receptors. To directly examine how dynein motors contribute to polarized dendritic transport, we established a trafficking assay in hippocampal neurons to selectively probe specific motor protein activity. This revealed that, unlike kinesins, dynein motors drive cargo selectively into dendrites, governed by their mixed microtubule array. Moreover, axon-specific cargos, such as presynaptic vesicle protein synaptophysin, are redirected to dendrites by coupling to dynein motors. Quantitative modeling demonstrated that bidirectional dynein-driven transport on mixed microtubules provides an efficient mechanism to establish a stable density of continuously renewing vesicles in dendrites. CONCLUSIONS These results demonstrate a powerful approach to study specific motor protein activity inside living cells and imply a key role for dynein in dendritic transport. We propose that dynein establishes the initial sorting of dendritic cargo and additional motor proteins assist in subsequent delivery.