An Introduction to Biomechanics

Humphrey, Jay D.; O’Rourke, Sherry L.

doi:10.1007/978-1-4939-2623-7

Cited by 18 publications

(7 citation statements)

References 43 publications

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“…3,22 PCO can be inhibited in vitro by using pharmaceutical agents targeting the cytoskeleton 23 ; the cytoskeleton is known to convey information about mechanical stresses on a cell to the nucleus resulting in changes in protein expression. 24 Together, these results suggest that LECs are strain-responsive cells (i.e., they can alter their behavior in response to mechanical cues from their environment). However, these studies have primarily focused on pathologic LEC differentiation leading to PCO and therefore did not examine whether proliferation rates or biomarker expression levels were directly influenced by mechanical stretching.…”

mentioning

confidence: 80%

Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Kumar

Chandler

Plageman

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The continuous growth of the lens throughout life may contribute to the onset of age-related conditions in the lens (i.e., presbyopia and cataract). Volumetric growth is the result of continuous proliferation of lens epithelial cells (LECs). The driving factors controlling LEC proliferation are not well understood. This study tested the hypothesis that mechanical stretching modulates LEC proliferation. METHODS. Biomechanical regulation of LEC proliferation was investigated by culturing whole porcine lenses and connective tissues ex vivo under varying physiologically relevant stretching conditions using a bespoke lens stretching device. Additionally, some lenses were treated with a YAP function inhibitor to determine the Hippo signaling pathway's role in regulating lens growth. Resulting changes in LEC labeling index were analyzed using EdU incorporation and flow cytometry for each lens. RESULTS. LEC proliferation was found to be modulated by mechanical strain. Increasing both the magnitude of static stretching and the stretching frequency in cyclic stretching resulted in a proportional increase in the labeling indices of the LECs. Additionally, treatment with the YAP function inhibitor effectively eliminated this relationship. CONCLUSIONS. These data demonstrate that LEC proliferation is regulated in part, by the mechanotransduction of stresses induced in the lens capsule and that YAP plays an important role in mechanosensing. These results have important implications for understanding lens growth and morphogenesis. The model may also be used to identify and evaluate targets for modulating lens growth.

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mentioning

confidence: 80%

Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Kumar

Chandler

Plageman

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…3) agrees with findings in preliminary rabbit studies by Maurice,29 which is expected due to the viscoelastic properties of the stroma. 40 Full-thickness porcine specimens exhibited approximately one-fifth less resistance to shear (G ¼ 0.38 kPa) compared to human specimens at 5% axial compression.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, there is a need to understand the mechanics of particularly adhesion molecules, that govern these interactions. 40 The stromal ground substance may thereby have an important role in treatment procedures, such as the photochemical modulation in CXL. The cornea shears readily in the tangential plane, which agrees with the layered, lamellar corneal architecture.…”

Section: Discussionmentioning

confidence: 99%

Corneal Resistance to Shear Force After UVA-Riboflavin Cross-Linking

Søndergaard¹,

Ivarsen²,

Hjortdal³

2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Søndergaard AP, Ivarsen A, Hjortdal J. Corneal resistance to shear force after UVA-riboflavin cross-linking. Invest Ophthalmol Vis Sci. 2013;54:5059-5069. DOI:10.1167/ iovs.12-10710 PURPOSE. We evaluated whether UVA-riboflavin collagen cross-linking (CXL) increases transverse stromal shear moduli ex vivo, whether the shear moduli are greater in the anterior compared to the posterior stroma, and whether the shear moduli are affected by CXL.METHODS. The resistance to unidirectional transverse shear of human (n ¼ 18) and porcine (n ¼ 42) corneas was measured in a custom engineered biaxial biomechanical setup at different hydrations. The corneas were separated into untreated, riboflavin solution-treated, and CXLtreated groups. The depth dependency of shear moduli within groups was assessed in femtosecond laser cut sheets. Dry weights were obtained for solids correction. RESULTS.In porcine full-thickness buttons and 300 lm anterior sheets, a significantly increased unidirectional transverse shear modulus was detected in riboflavin-treated and CXL-treated groups compared to the respective untreated groups. There was no significant difference in shear modulus between riboflavin-and CXL-treated groups. In all groups, the shear moduli were greater in the anterior sheets compared to posterior sheets. Similar results were detected in human corneas. CONCLUSIONS.A method for unidirectional transverse shear resistance measurement was developed. The shear moduli were greater in the anterior compared to the posterior sheets. Increase in shear moduli was observed in the riboflavin and CXL groups compared to the untreated group, indicating that the immediate effects of the riboflavin or CXL treatment may be due partly to ground substance/dextran-5-phosphate interaction.Keywords: cornea, riboflavin, UVA, cross-linking, CXL, collagen, swelling pressure, shear force, shear modulus, biomechanics T he corneal stroma is a very dense matrix composed of several hundred sheets of highly organized collagen lamellae, stacked on each other preferably in parallel with respect to the corneal surface. Within a given lamella, the majority of fibrils lie parallel to each other and to the corneal surface, but at large angles with those in adjacent lamella. Overall, they are found at all angles within the corneal plane. Anterior and midstromal lamellae bifurcate and interweave, 1 whereas posterior lamellae tend to lie noninterwoven in stacked layers.2 The collagen fibrils in the central cornea have preferred directions in the inferior-superior and nasal-temporal meridians in the posterior two-thirds, whereas the anterior third is arranged more isotropically. 3,4 This microstructure of the corneal stroma suggests that its elasticity will depend on direction during mechanical testing (anisotropy) and that the in-plane properties will be different from the transverse properties.5-7 The cornea shears readily in the tangential plane without separating, even at high shear deformations. 8,9 Thus, the stroma possesses self-cohesion between c...

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“…MTC is similar to AFM except that one either affixes onto or embeds within a living cell a ferromagnetic bead that can be cyclically twisted using a magnetic field. Associated data are often interpreted in terms of the so-called storage (G 0 ) and loss (G 00 ) shear moduli, which are basic descriptors of a one-dimensional (1D) linearly viscoelastic behavior over small strains and rotations [32]. For example, MTC was used to show that the stiffness of vascular smooth muscle cells (i.e., elastic storage and dissipative loss moduli) increases in aging [33].…”

Section: Approachesmentioning

confidence: 99%

Arterial Stiffness: Different Metrics, Different Meanings

Spronck

Humphrey

2019

Journal of Biomechanical Engineering

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Findings from basic science and clinical studies agree that arterial stiffness is fundamental to both the mechanobiology and the biomechanics that dictate vascular health and disease. There is, therefore, an appropriately growing literature on arterial stiffness. Perusal of the literature reveals, however, that many different methods and metrics are used to quantify arterial stiffness, and reported values often differ by orders of magnitude and have different meanings. Without clear definitions and an understanding of possible inter-relations therein, it is increasingly difficult to integrate results from the literature to glean true understanding. In this paper, we briefly review methods that are used to infer values of arterial stiffness that span studies on isolated cells, excised intact vessels, and clinical assessments. We highlight similarities and differences and identify a single theoretical approach that can be used across scales and applications and thus could help to unify future results. We conclude by emphasizing the need to move toward a synthesis of many disparate reports, for only in this way will we be able to move from our current fragmented understanding to a true appreciation of how vascular cells maintain, remodel, or repair the arteries that are fundamental to cardiovascular properties and function.

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An Introduction to Biomechanics

Cited by 18 publications

References 43 publications

Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Lens Stretching Modulates Lens Epithelial Cell Proliferation via YAP Regulation

Corneal Resistance to Shear Force After UVA-Riboflavin Cross-Linking

Arterial Stiffness: Different Metrics, Different Meanings

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