Biomedical subjects

J Pablo Marquez

Publications and source records attributed to J Pablo Marquez.

5 recordsLinked to original sources

PubMed2006

Cellular and matrix contributions to tissue construct stiffness increase with cellular concentration.

The mechanics of bio-artificial tissue constructs result from active and passive contributions of cells and extracellular matrix (ECM). We delineated these for a fibroblast-populated matrix (FPM) consisting of chick embryo fibroblast cells in a type I collagen ECM through mechanical testing, mechanical modeling, and selective biochemical elimination of tissue components. From a series of relaxation tests, we found that contributions to overall tissue mechanics from both cells and ECM increase exponentially with the cell concentration. The force responses in these relaxation tests exhibited a logarithmic decay over the 3600 second test duration. The amplitudes of these responses were nearly linear with the amplitude of the applied stretch. The active component of cellular forces rose dramatically for FPMs containing higher cell concentrations.

Animals↗

PubMed2006

Reconstitution of the Frank-Starling mechanism in engineered heart tissues.

According to the Frank-Starling mechanism, as the heart is stretched, it increases its contraction force. Reconstitution of the Frank-Starling mechanism is an important milestone for producing functional heart tissue constructs. Spontaneously contracting engineered heart tissues (EHTs) were reconstituted by growing dissociated chicken embryo cardiomyocytes in collagen matrices. Twitch and baseline tensions were recorded at precisely controlled levels of tissue strain. The EHTs showed a steep increase in twitch tension from 0.47 +/- 0.02 to 0.91 +/- 0.02 mN/mm2 as they were stretched at a constant rate (2.67% per min) from 86% to 100% of the length at which maximum twitch force was exerted. In response to a sudden stretch (3.3%), the twitch tension increased gradually (approximately 60 s) in a Gd3+-sensitive manner, suggesting the presence of stretch-activated Ca2+ channels. A large difference in baseline tension between lengthening (loading) and shortening (unloading) was also recorded. Disruption of nonsarcomeric actin filaments by cytochalasin D and latrunculin B decreased this difference. A simple mechanical model interprets these results in terms of mechanical connections between myocytes and nonmuscle cells. The experimental results strongly suggest that regulation of twitch tension in EHTs is similar to that of natural myocardium.

Animals↗

PubMed2005

On the application of strain factors for approximation of the contribution of anisotropic cells to the mechanics of a tissue construct.

Bio-artificial tissue constructs consisting of fibroblast cells embedded in a collagenous matrix are valuable in vitro systems in which to study cellular mechanics. Deriving cellular mechanics from the results of experimentation on tissue constructs requires a mathematical relationship that delineates amongst the contributions of the constituents of a tissue construct. A scaling between the average strain in a uniformly stretched tissue and the axial strain in isotropic cells was used in earlier work to study relations between cell mechanics and the overall mechanics of a tissue construct. That work showed that a scaling factor called a "strain factor" provided an accurate representation of the average axial strain in isotropic cells. The present study analyzes such relationships for anisotropic cells. We incorporate Eshelby's (1957; Proceedings of the Royal Society of London A 241, 376; 1959; Proceedings of the Royal Society of London A 252, 561) exact solution for the strain field in isolated ellipsoidal inclusions into the Zahalak (Biophysical journal 79, 2369) constitutive model for tissue constructs. Results showed that, for the case of prolate cells, the strain along the major cell axis is mostly influenced by the remote strain projected along that axis; off-axis cell mechanics plays only a small role in most tissues. The strain factor approximation is shown to be accurate for anisotropic cells to within a few percent for the vast majority of tissues. The results presented in this paper provide an explicit measure of the effects of cellular anisotropy, and a mechanism for calculating the contributions of these effects to overall tissue mechanics when these effects are important.

Anisotropy↗

PubMed2004

Thin bio-artificial tissues in plane stress: the relationship between cell and tissue strain, and an improved constitutive model.

Constitutive models are needed to relate the active and passive mechanical properties of cells to the overall mechanical response of bio-artificial tissues. The Zahalak model attempts to explicitly describe this link for a class of bio-artificial tissues. A fundamental assumption made by Zahalak is that cells stretch in perfect registry with a tissue. We show this assumption to be valid only for special cases, and we correct the Zahalak model accordingly. We focus on short-term and very long-term behavior, and therefore consider tissue constituents that are linear in their loading response (although not necessarily linear in unloading). In such cases, the average strain in a cell is related to the macroscopic tissue strain by a scalar we call the "strain factor". We incorporate a model predicting the strain factor into the Zahalak model, and then reinterpret experiments reported by Zahalak and co-workers to determine the in situ stiffness of cells in a tissue construct. We find that, without the modification in this article, the Zahalak model can underpredict cell stiffness by an order of magnitude.

Animals↗

PubMed2004

The relationship between cell and tissue strain in three-dimensional bio-artificial tissues.

Continuum constitutive laws are needed to ensure that bio-artificial tissue constructs replicate the mechanical response of the tissues they replace, and to understand how the constituents of these constructs contribute to their overall mechanical response. One model designed to achieve both of these aims is the Zahalak model, which was modified by Marquez and co-workers to incorporate inhomogeneous strain fields within very thin tissues. When applied to reinterpret previous measurements, the modified Zahalak model predicted higher values of the continuum stiffness of fibroblasts than earlier estimates. In this work, we further modify the Zahalak model to account for inhomogeneous strain fields in constructs whose cell orientations have a significant out-of-plane component. When applied to reinterpret results from the literature, the new model shows that estimates of continuum cell stiffness might need to be revised upward. As in this article's companion, we updated the average cell strain by defining a correction factor ("strain factor"), based upon the elastic response. Three different cell orientation distributions were studied. We derived an approximate scaling model for the strain factor, and validated it against exact and self-consistent (mean-field) solutions from the literature for dilute cell concentrations, and Monte Carlo simulations involving three-dimensional finite element analyses for high cell concentrations.

Animals↗