Why Microtubules run in Circles - Mechanical Hysteresis of the Tubulin Lattice

The fate of every eukaryotic cell subtly relies on the exceptional mechanical properties of microtubules. Despite significant efforts, understanding their unusual mechanics remains elusive. One persistent, unresolved mystery is the formation of long-lived arcs and rings, e.g. in kinesin-driven gliding assays. To elucidate their physical origin we develop a model of the inner workings of the microtubule's lattice, based on recent experimental evidence for a conformational switch of the tubulin dimer. We show that the microtubule lattice itself coexists in discrete polymorphic states. Curved states can be induced via a mechanical hysteresis involving torques and forces typical of few molecular motors acting in unison. This lattice switch renders microtubules not only virtually unbreakable under typical cellular forces, but moreover provides them with a tunable response integrating mechanical and chemical stimuli.Comment: 5 pages, 4 Movies in the Supplemen

A mathematical model for mechanically-induced deterioration of the binder in lithium-ion electrodes

This study is concerned with modeling detrimental deformations of the binder phase within lithium-ion batteries that occur during cell assembly and usage. A two-dimensional poroviscoelastic model for the mechanical behavior of porous electrodes is formulated and posed on a geometry corresponding to a thin rectangular electrode, with a regular square array of microscopic circular electrode particles, stuck to a rigid base formed by the current collector. Deformation is forced both by (i) electrolyte absorption driven binder swelling, and; (ii) cyclic growth and shrinkage of electrode particles as the battery is charged and discharged. The governing equations are upscaled in order to obtain macroscopic effective-medium equations. A solution to these equations is obtained, in the asymptotic limit that the height of the rectangular electrode is much smaller than its width, that shows the macroscopic deformation is one-dimensional. The confinement of macroscopic deformations to one dimension is used to obtain boundary conditions on the microscopic problem for the deformations in a 'unit cell' centered on a single electrode particle. The resulting microscale problem is solved using numerical (finite element) techniques. The two different forcing mechanisms are found to cause distinctly different patterns of deformation within the microstructure. Swelling of the binder induces stresses that tend to lead to binder delamination from the electrode particle surfaces in a direction parallel to the current collector, whilst cycling causes stresses that tend to lead to delamination orthogonal to that caused by swelling. The differences between the cycling-induced damage in both: (i) anodes and cathodes, and; (ii) fast and slow cycling are discussed. Finally, the model predictions are compared to microscopy images of nickel manganese cobalt oxide cathodes and a qualitative agreement is found.Comment: 25 pages, 11 figure

Designing Biomimetic Implant Surfaces to Promote Osseointegration under Osteoporotic Conditions by Revitalizing Mechanisms Coupling Bone Resorption to Formation

In cases of compromised bone remodeling like osteoporosis, insufficient osseointegration occurs and results in implant failure. Implant retention relies on proper secondary fixation, which is developed during bone remodeling. This process is disrupted in metastatic bone diseases like osteoporosis. Osteoporosis is characterized low bone mass and bone strength resulting from either accelerated osteoclast-mediated bone resorption or impaired osteoblast-mediated bone formation. These two processes are not independent phenomena. In fact, osteoporosis can be viewed as a breakdown of the cellular communication connecting bone resorption to bone formation. Because bone remodeling occurs at temporally generated specific anatomical sites and at different times, local regulators that control cross-talk among the cells of the BRU are important. Previous studies show Ti implant surface characteristics like roughness, hydrophilicity, and chemistry influence the osteoblastic differentiation of human MSCs and maturation of OBs. Furthermore, microstructured Ti surfaces modulate the production of factors shown to be important in the reciprocal communication necessary for the maintenance of healthy bone remodeling. Semaphorin signaling proteins are known to couple the communication of osteoblasts to osteoclasts and are capable of stimulating bone formation or bone resorption depending on certain cues. Implant surface properties can be optimized to exploit these effects to favor rapid osseointegration in patients with osteoporosis

Bone and metal - an orthopaedic perspective on osseointegration of metals

The area of implant osseointegration is of major importance, given the predicted significant rise in the number of orthopaedic procedures and an increasingly ageing population. Osseointegration is a complex process involving a number of distinct mechanisms affected by the implant bulk properties and surface characteristics. Our understanding and ability to modify these mechanisms through alterations in implant design is continuously expanding. The following review considers the main aspects of material and surface alterations in metal implants, and the extent of their subsequent influence on osseointegration. Clinically, osseointegration results in asymptomatic stable durable fixation of orthopaedic implants. The complexity of achieving this outcome through incorporation and balance of contributory factors is highlighted through a clinical case report

Frequency-Driven Crack Propagation in Ultrasonically-Assisted Bone Cutting

Ultrasonically-assisted bone cutting with high precision has many advantages for orthopedic surgeries. However, irregular crack propagation, large fractured chips, and surface damage may occur during the cutting process due to the brittleness and anisotropy of cortical bone. These can be minimized by optimizing the operating parameters of the cutting tool; cutting frequency, amplitude, speed, depth, and temperature, in consideration of the toughening mechanism of bone. Therefore, the current study is motivated to investigate the effect of varying frequency on crack propagation in ultrasonically-assisted bone cutting through the means of finite element analysis. The pattern of crack propagation in relation to the variation of frequencies was investigated using the extended finite element method (XFEM) in consideration of the bone microstructures. The results showed that crack propagation is effectively controlled when the tool is operated at higher frequencies, but an up-forward crack propagation following the trajectory of tool vibration is only apparent at frequencies higher than 800 Hz. Neglecting the operating outputs at 2400 Hz, the induced force and stress are observed to decrease proportionally with increasing frequency

Frequency-Driven Crack Propagation in Ultrasonically-Assisted Bone Cutting

Ultrasonically-assisted bone cutting with high precision has many advantages for orthopedic surgeries. However, irregular crack propagation, large fractured chips, and surface damage may occur during the cutting process due to the brittleness and anisotropy of cortical bone. These can be minimized by optimizing the operating parameters of the cutting tool; cutting frequency, amplitude, speed, depth, and temperature, in consideration of the toughening mechanism of bone. Therefore, the current study is motivated to investigate the effect of varying frequency on crack propagation in ultrasonically-assisted bone cutting through the means of finite element analysis. The pattern of crack propagation in relation to the variation of frequencies was investigated using the extended finite element method (XFEM) in consideration of the bone microstructures. The results showed that crack propagation is effectively controlled when the tool is operated at higher frequencies, but an up-forward crack propagation following the trajectory of tool vibration is only apparent at frequencies higher than 800 Hz. Neglecting the operating outputs at 2400 Hz, the induced force and stress are observed to decrease proportionally with increasing frequency

Design of Tribologically Enhanced Polymeric Materials for Biomedical Applications

Anytime two surfaces are in normal contact, accompanied by tangential motion, there is potential for deterioration of one or both surfaces. Gradual wear, or the removal of surface material, is typically an undesirable event. Therefore, the need for lubrication arises to minimize the amount of shear stress that develops between opposing surfaces. This reduction in shear stress is characterized by the coefficient of friction (COF). Friction is one of the primary subjects of interest in tribology, the science of the friction and wear of articulating surfaces. A number of fascinating tribological systems can be found in nature. One example which has drawn a considerable interest is articular cartilage. This smooth white tissue lines the articulating surfaces of our joints and sustains a tremendous amount of stress while maintaining smooth joint motion and low COF. The low COF exhibited by articular cartilage is unmatched by any man-made material. The phenomenal tribological properties of this biphasic material are attributed to a combination of a unique boundary lubrication mechanism and its ability to support interstitial fluid pressurization This dissertation details the synthesis and characterization of novel tribologically enhanced polymeric materials which show great potential for several biomedical applications. Design of these material relied on the use of biomimetic tribological mechanisms. The overarching characterization described in this investigation provides valuable insight into the physical and mechanical characteristics of these unique materials

In-vitro study of the bioactivity and cytotoxicity response of Ti surfaces modified by Nb and Mo diffusion treatments

This work focuses on the bioactivity and biological response of modified Ti surfaces produced by powder metallurgy. They are processed by diffusion of two beta-stabilizing elements, Nb and Mo, deposited onto the surface of PM Ti substrates. Moreover, the addition of an activating agent, NH4Cl, to the suspension has been carried out by thermo-reactive diffusion process. The surface modification led to a gradient in composition (Ti-Nb or Ti-Mo) and microstructure (beta / alpha + beta / alpha phases). This work presents the bioactivity results of these Ti-Mo and Ti-Nb surfaces as well as the cell-material response of the Ti-Nb surfaces. The reactivity of the materials was tested through immersion in simulated body fluid considering Ca and P precipitation in order to assess the ability of the materials to induce hydroxyapatite formation. The in-vitro cell response was evaluated by human osteoblast-like cells incubation on the different surfaces for 48 h. The investigation led to positive results in terms of surface bioactivity and an improved cell-material interaction of the PM modified Ti-Nb surfaces compared to the reference Ti material.The authors would like to thank the funding provided for this research by the Regional Government of Madrid (program MULTIMAT-CHALLENGE-CM, ref. S2013/MIT-2862), and by the University Carlos III of Madrid for the research stay of three months in the Institute of Biomaterials (University of Erlangen-Nurnberg)

Locally Administrated Perindopril Improves Healing in an Ovariectomized Rat Tibial Osteotomy Model

Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX), tibial fractures were produced in Sprague–Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day) was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01), and the bone volume over total volume (BV/TV) increased by 29.9% and 24.3% (p<0.01) at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats