In single-cell analysis, cellular activity and parameters are assayed on an individual, rather than population-average basis. Essential to observing the activity of these cells over time is the ...ability to trap, pattern and retain them, for which previous single-cell-patterning work has principally made use of mechanical methods. While successful as a long-term cell-patterning strategy, these devices remain essentially single use. Here we introduce a new method for the patterning of multiple spatially separated single particles and cells using high-frequency acoustic fields with one cell per acoustic well. We characterize and demonstrate patterning for both a range of particle sizes and the capture and patterning of cells, including human lymphocytes and red blood cells infected by the malarial parasite Plasmodium falciparum. This ability is made possible by a hitherto unexplored regime where the acoustic wavelength is on the same order as the cell dimensions.
The objective of this study was to investigate whether the two most common growth mechanics modeling frameworks, the constrained-mixture growth model and the kinematic growth model, could be ...reconciled mathematically. The purpose of this effort was to provide practical guidelines for potential users of these modeling frameworks. Results showed that the kinematic growth model is mathematically consistent with a special form of the constrained-mixture growth model, where only one generation of a growing solid exists at any given time, overturning its entire solid mass at each instant of growth in order to adopt the reference configuration dictated by the growth deformation. The thermodynamics of the kinematic growth model, along with the specialized constrained-mixture growth model, requires a cellular supply of chemical energy to allow deposition of solid mass under a stressed state. A back-of-the-envelope calculation shows that the amount of chemical energy required to sustain biological growth under these models is negligibly small, when compared to the amount of energy normally consumed daily by the human body. In conclusion, this study successfully reconciled the two most popular growth theories for biological growth and explained the special circumstances under which the constrained-mixture growth model reduces to the kinematic growth model.
In this erratum, we correct a mistake in a subcomponent of the numerical algorithm proposed in our recent study for modeling anisotropic reactive nonlinear viscoelasticity (doi:10.1115/1.4054983), ...for the special case where multiple weak bond families may be recruited with loading. This correction overcomes a nonphysical response noted under uni-axial cyclical loading.
Collagen forms fibrous networks that reinforce tissues and provide an extracellular matrix for cells. These networks exhibit remarkable strain-stiffening properties that tailor the mechanical ...functions of tissues and regulate cell behavior. Recent models explain this nonlinear behavior as an intrinsic feature of disordered networks of stiff fibers. Here, we experimentally validate this theoretical framework by measuring the elastic properties of collagen networks over a wide range of self-assembly conditions. We show that the model allows us to quantitatively relate both the linear and nonlinear elastic behavior of collagen networks to their underlying architecture. Specifically, we identify the local coordination number (or connectivity) 〈z〉 as a key architectural parameter that governs the elastic response of collagen. The network elastic response reveals that 〈z〉 decreases from 3.5 to 3 as the polymerization temperature is raised from 26 to 37°C while being weakly dependent on concentration. We furthermore infer a Young’s modulus of 1.1 MPa for the collagen fibrils from the linear modulus. Scanning electron microscopy confirms that 〈z〉 is between three and four but is unable to detect the subtle changes in 〈z〉 with polymerization conditions that rheology is sensitive to. Finally, we show that, consistent with the model, the initial stress-stiffening response of collagen networks is controlled by the negative normal stress that builds up under shear. Our work provides a predictive framework to facilitate future studies of the regulatory effect of extracellular matrix molecules on collagen mechanics. Moreover, our findings can aid mechanobiological studies of wound healing, fibrosis, and cancer metastasis, which require collagen matrices with tunable mechanical properties.
Cells can detect and react to the biophysical properties of the extracellular environment through integrin-based adhesion sites and adapt to the extracellular milieu in a process called ...mechanotransduction. At these adhesion sites, integrins connect the extracellular matrix (ECM) with the F-actin cytoskeleton and transduce mechanical forces generated by the actin retrograde flow and myosin II to the ECM through mechanosensitive focal adhesion proteins that are collectively termed the "molecular clutch." The transmission of forces across integrin-based adhesions establishes a mechanical reciprocity between the viscoelasticity of the ECM and the cellular tension. During mechanotransduction, force allosterically alters the functions of mechanosensitive proteins within adhesions to elicit biochemical signals that regulate both rapid responses in cellular mechanics and long-term changes in gene expression. Integrin-mediated mechanotransduction plays important roles in development and tissue homeostasis, and its dysregulation is often associated with diseases.
In epithelial cancers, cells must invade through basement membranes (BMs) to metastasize. The BM, a thin layer of extracellular matrix underlying epithelial and endothelial tissues, is primarily ...composed of laminin and collagen IV and serves as a structural barrier to cancer cell invasion, intravasation, and extravasation. BM invasion has been thought to require protease degradation since cells, which are typically on the order of 10 µm in size, are too large to squeeze through the nanometer-scale pores of the BM. However, recent studies point toward a more complex picture, with physical forces generated by cancer cells facilitating protease-independent BM invasion. Moreover, collective cell interactions, proliferation, cancer-associated fibroblasts, myoepithelial cells, and immune cells are all implicated in regulating BM invasion through physical forces. A comprehensive understanding of BM structure and mechanics and diverse modes of BM invasion may yield new strategies for blocking cancer progression and metastasis.
Standard treatment in cases of progressive keratectasia is UV-triggered corneal cross-linking. For irradiances larger than 10 mW/cm(2) and treatment times below 10 minutes, the scientific proof of a ...biomechanical strengthening effect is insufficient. The authors investigated the biomechanical strengthening of ex vivo corneal tissue treated with irradiances between 3 mW/cm(2) and 90 mW/cm(2) and illumination times from 30 minutes to 1 minute, respectively.
A total of 100 porcine eyes received riboflavin + UV treatment (constant irradiation dose of 5.4 J/cm(2)) with different intensities and illumination times and were randomly assigned into 10 groups. A control group (80 eyes) was not irradiated but underwent the same treatment otherwise. Young's modulus at 10% strain was determined for each strip after uniaxial stress-strain measurement. A Kruskal-Wallis test was used for statistical analysis.
A statistically significant difference (α = 0.01) was found between the median value of Young's modulus of the treatment groups up to 45 mW/cm(2) (illumination times from 30 minutes to 2 minutes) compared with the control group. There was no statistically significant difference between the treatment groups from 50 mW/cm(2) up to 90 mW/cm(2) (illumination times of less than 2 minutes) and the control group.
The ex vivo results of corneal cross-linking performed in porcine corneas show that the Bunsen-Roscoe reciprocity law is only valid for illumination intensities up to 40 to 50 mW/cm(2) and illumination times of more than 2 minutes. Further experiments are necessary to validate these results for in vivo human corneal tissue. Additionally, safety aspects at high intensities must be investigated.
Irregular biomechanics are a hallmark of cancer biology subject to extensive study. The mechanical properties of a cell are similar to those of a material. A cell's resistance to stress and strain, ...its relaxation time, and its elasticity are all properties that can be derived and compared to other types of cells. Quantifying the mechanical properties of cancerous (malignant) versus normal (non-malignant) cells allows researchers to further uncover the biophysical fundamentals of this disease. While the mechanical properties of cancer cells are known to consistently differ from the mechanical properties of normal cells, a standard experimental procedure to deduce these properties from cells in culture is lacking. This paper outlines a procedure to quantify the mechanical properties of single cells in vitro using a fluid shear assay. The principle behind this assay involves applying fluid shear stress onto a single cell and optically monitoring the resulting cellular deformation over time. Cell mechanical properties are subsequently characterized using digital image correlation (DIC) analysis and fitting an appropriate viscoelastic model to the experimental data generated from the DIC analysis. Overall, the protocol outlined here aims to provide a more effective and targeted method for the diagnosis of difficult-to-treat cancers.
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