Viscoelastic polyacrylamide MR elastography phantoms with tunable damping ratio independent of shear stiffness.

Physiologically modeled test samples with known properties and characteristics, or phantoms, are essential for developing sensitive, repeatable, and accurate quantitative MRI techniques. Magnetic resonance elastography (MRE) is one such technique used to estimate tissue mechanical properties, and it is advantageous to use phantoms with independently tunable mechanical properties to benchmark the accuracy of MRE methods. Phantoms with tunable shear stiffness are commonly used for MRE, but tuning the viscosity or damping ratio has proven to be difficult.

Enzymatic digestion does not compromise sliding-mediated cartilage lubrication.

Articular cartilage's remarkable low-friction properties are essential to joint function. In osteoarthritis (OA), cartilage degeneration (e.g.

Exogenous Collagen Crosslinking is Highly Detrimental to Articular Cartilage Lubrication.

Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear.

Biomechanical Impact of Pathogenic MYBPC3 Truncation Variant Revealed by Dynamically Tuning In Vitro Afterload.

Engineered cardiac microtissues were fabricated using pluripotent stem cells with a hypertrophic cardiomyopathy associated c. 2827 C>T; p.R943x truncation variant in myosin binding protein C (MYBPC3).

The effect of polymer stiffness on magnetization reversal of magnetorheological elastomers.

Ultrasoft magnetorheological elastomers (MREs) offer convenient real-time magnetic field control of mechanical properties that provides a means to mimic mechanical cues and regulators of cells . Here, we systematically investigate the effect of polymer stiffness on magnetization reversal of MREs using a combination of magnetometry measurements and computational modeling. Poly-dimethylsiloxane-based MREs with Young's moduli that range over two orders of magnitude were synthesized using commercial polymers Sylgard 527, Sylgard 184, and carbonyl iron powder.

Biomimetic Substrate to Probe Dynamic Interplay of Topography and Stiffness on Cardiac Fibroblast Activation.

Materials with the ability to change properties can expand the capabilities of models of biological processes and diseases as it has become increasingly clear that static, stiff materials with smooth surfaces fall short in recapitulating the cellular microenvironment. Here, we introduce a patterned material that can be rapidly stiffened and softened in response to an external magnetic field through the addition of magnetic inclusions into a soft silicone elastomer with topographic surface patterning. This substrate can be used for cell culture to investigate short-term cellular responses to dynamic stiffening or softening and the interaction with topography that encourages cells to assume a specific morphology.

Extracellular stiffness induces contractile dysfunction in adult cardiomyocytes via cell-autonomous and microtubule-dependent mechanisms.

The mechanical environment of the myocardium has a potent effect on cardiomyocyte form and function, yet an understanding of the cardiomyocyte responses to extracellular stiffening remains incomplete. We therefore employed a cell culture substrate with tunable stiffness to define the cardiomyocyte responses to clinically relevant stiffness increments in the absence of cell-cell interactions. When cultured on substrates magnetically actuated to mimic the stiffness of diseased myocardium, isolated rat adult cardiomyocytes exhibited a time-dependent reduction of sarcomere shortening, characterized by slowed contraction and relaxation velocity, and alterations of the calcium transient.

Magnetic field tuning of mechanical properties of ultrasoft PDMS-based magnetorheological elastomers for biological applications.

We report tuning of the moduli and surface roughness of magnetorheological elastomers (MREs) by varying applied magnetic field. Ultrasoft MREs are fabricated using a physiologically relevant commercial polymer, Sylgard 527, and carbonyl iron powder (CIP). We found that the shear storage modulus, Young's modulus, and root-mean-square surface roughness are increased by ~41×, ~11×, and ~11×, respectively, when subjected to a magnetic field strength of 95.

Simultaneous time-varying viscosity, elasticity, and mass measurements of single adherent cancer cells across cell cycle.

Biophysical studies on single cells have linked cell mechanics to physiology, functionality and disease. Evaluation of mass and viscoelasticity versus cell cycle can provide further insights into cell cycle progression and the uncontrolled proliferation of cancer. Using our pedestal microelectromechanical systems resonant sensors, we have developed a non-contact interferometric measurement technique that simultaneously tracks the dynamic changes in the viscoelastic moduli and mass of adherent colon (HT-29) and breast cancer (MCF-7) cells from the interphase through mitosis and then to the cytokinesis stages of their growth cycle.

Tunable and Reversible Substrate Stiffness Reveals a Dynamic Mechanosensitivity of Cardiomyocytes.

New directions in material applications have allowed for the fresh insight into the coordination of biophysical cues and regulators. Although the role of the mechanical microenvironment on cell responses and mechanics is often studied, most analyses only consider static environments and behavior, however, cells and tissues are themselves dynamic materials that adapt in myriad ways to alterations in their environment. Here, we introduce an approach, through the addition of magnetic inclusions into a soft poly(dimethylsiloxane) elastomer, to fabricate a substrate that can be stiffened nearly instantaneously in the presence of cells through the use of a magnetic gradient to investigate short-term cellular responses to dynamic stiffening or softening.

Aligning Synthetic Hippocampal Neural Circuits via Self-Rolled-Up Silicon Nitride Microtube Arrays.

Directing neurons to form predetermined circuits with the intention of treating neurological disorders and neurodegenerative diseases is a fundamental goal and current challenge in neuroengineering. Until recently, only neuronal aggregates were studied and characterized in culture, which can limit information gathered to populations of cells. In this study, we use a substrate constructed of arrays of strain-induced self-rolled-up membrane 3D architectures.

Increased Afterload Augments Sunitinib-Induced Cardiotoxicity in an Engineered Cardiac Microtissue Model.

Sunitinib, a multitargeted oral tyrosine kinase inhibitor, used widely to treat solid tumors, results in hypertension in up to 47% and left ventricular dysfunction in up to 19% of treated individuals. The relative contribution of afterload toward inducing cardiac dysfunction with sunitinib treatment remains unknown. We created a preclinical model of sunitinib cardiotoxicity using engineered microtissues that exhibited cardiomyocyte death, decreases in force generation, and spontaneous beating at clinically relevant doses.

Optomechanical microrheology of single adherent cancer cells.

There is a close relationship between the mechanical properties of cells and their physiological function. Non-invasive measurements of the physical properties of cells, especially of adherent cells, are challenging to perform. Through a non-contact optical interferometric technique, we measure and combine the phase, amplitude, and frequency of vibrating silicon pedestal micromechanical resonant sensors to quantify the "loss tangent" of individual adherent human colon cancer cells (HT-29).

Mechanically dynamic PDMS substrates to investigate changing cell environments.

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g.

Evidence of differential mass change rates between human breast cancer cell lines in culture.

Investigating the growth signatures of single cells will determine how cell growth is regulated and cell size is maintained. The ability to precisely measure such changes and alterations in cell size and cell mass could be important for applications in cancer and drug screening. Here, we measure the mass growth rate of individual benign (MCF-10A), non-invasive (MCF-7), and highly-invasive malignant (MDA-MB-231) breast cancer cells.

Optomechanical measurement of the stiffness of single adherent cells.

Recent advances in mechanobiology have accumulated strong evidence showing close correlations between the physiological conditions and mechanical properties of cells. In this paper, a novel optomechanical technique to characterize the stiffness of single adherent cells attached on a substrate is reported. The oscillation in a cell's height on a vertically vibrating reflective substrate is measured with a laser Doppler vibrometer as apparent changes in the phase of the measured velocity.

Slowing DNA Transport Using Graphene-DNA Interactions.

Slowing down DNA translocation speed in a nanopore is essential to ensuring reliable resolution of individual bases. Thin membrane materials enhance spatial resolution but simultaneously reduce the temporal resolution as the molecules translocate far too quickly. In this study, the effect of exposed graphene layers on the transport dynamics of both single (ssDNA) and double-stranded DNA (dsDNA) through nanopores is examined.

Biophysical properties of human breast cancer cells measured using silicon MEMS resonators and atomic force microscopy.

Biophysical studies on individual cells can help to establish the relationship between mechanics and biological function. In the case of cancer, mechanical properties of cells have been linked to metastatic activity and disease progression and can be crucial for understanding cellular physiology and metabolism. In this study, we report measurements of the stiffness of breast cancer cells using a novel silicon MEMS resonant sensor and validated the results with atomic force microscopy (AFM).

Measuring physical properties of neuronal and glial cells with resonant microsensors.

Microelectromechanical systems (MEMS) resonant sensors provide a high degree of accuracy for measuring the physical properties of chemical and biological samples. These sensors enable the investigation of cellular mass and growth, though previous sensor designs have been limited to the study of homogeneous cell populations. Population heterogeneity, as is generally encountered in primary cultures, reduces measurement yield and limits the efficacy of sensor mass measurements.

Dissolution chemistry and biocompatibility of single-crystalline silicon nanomembranes and associated materials for transient electronics.

Single-crystalline silicon nanomembranes (Si NMs) represent a critically important class of material for high-performance forms of electronics that are capable of complete, controlled dissolution when immersed in water and/or biofluids, sometimes referred to as a type of "transient" electronics. The results reported here include the kinetics of hydrolysis of Si NMs in biofluids and various aqueous solutions through a range of relevant pH values, ionic concentrations and temperatures, and dependence on dopant types and concentrations. In vitro and in vivo investigations of Si NMs and other transient electronic materials demonstrate biocompatibility and bioresorption, thereby suggesting potential for envisioned applications in active, biodegradable electronic implants.

Micro-patterning of mammalian cells on suspended MEMS resonant sensors for long-term growth measurements.

MEMS resonant mass sensors can measure the mass of individual cells, though long-term growth measurements are limited by the movement of cells off the sensor area. Micro-patterning techniques are a powerful approach to control the placement of individual cells in an arrayed format. In this work we present a method for micro-patterning cells on fully suspended resonant sensors through select functionalization and passivation of the chip surface.

Micromechanical properties of hydrogels measured with MEMS resonant sensors.

Hydrogels have gained wide usage in a range of biomedical applications because of their biocompatibility and the ability to finely tune their properties, including viscoelasticity. The use of hydrogels on the microscale is increasingly important for the development of drug delivery techniques and cellular microenvironments, though the ability to accurately characterize their micromechanical properties is limited. Here we demonstrate the use of microelectromechanical systems (MEMS) resonant sensors to estimate the properties of poly(ethylene glycol) diacrylate (PEGDA) microstructures over a range of concentrations.

Characterization of mass and swelling of hydrogel microstructures using MEMS resonant mass sensor arrays.

The use of hydrogels for biomedical engineering, and for the development of biologically inspired cellular systems at the microscale, is advancing at a rapid pace. Microelectromechanical system (MEMS) resonant mass sensors enable the mass measurement of a range of materials. The integration of hydrogels onto MEMS resonant mass sensors is demonstrated, and these sensors are used to characterize the hydrogel mass and swelling characteristics.

Self-heating in piezoresistive cantilevers.

We report experiments and models of self-heating in piezoresistive microcantilevers that show how cantilever measurement resolution depends on the thermal properties of the surrounding fluid. The predicted cantilever temperature rise from a finite difference model is compared with detailed temperature measurements on fabricated devices. Increasing the fluid thermal conductivity allows for lower temperature operation for a given power dissipation, leading to lower force and displacement noise.

A microcantilever heater-thermometer with a thermal isolation layer for making thermal nanotopography measurements.

This paper presents a microcantilever having a microscale heater-thermometer fabricated from doped single crystal silicon that is mounted on a silicon nitride thermal isolation structure. The silicon nitride isolation structure is in turn connected to doped single crystal silicon legs. The cantilever fabrication, its characterization, and its application in thermal nanotopography measurements are presented in this work.