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Biomedical subjects

R Skalak

Publications and source records attributed to R Skalak.

At least 73 records · Page 4Linked to original sources
PubMed1984

Biomechanics at the cellular level. The ALZA distinguished lecture.

The mechanical behavior of individual cells presents a variety of problems of interest in many different biologic phenomena. The rheology of single red blood cells is well developed, and passive properties of leukocytes and endothelial cells are currently being explored. Dynamic aspects of single-cell mechanics, including growth, cell division, active motion, contractile mechanisms, phagocytosis, and locomotion, offer many challenging aspects to be analyzed. Transduction mechanisms of neurosensory cells and mechanical stresses and damage of neural structures are relatively unexplored.

Animals↗
PubMed1984

An allometric network model of craniofacial growth.

This study of cranial skeletal growth kinematics details the conceptual principles underlying the development of an allometric network model of such growth. This model is tested by the analysis of longitudinal rat and cross-sectional human growth data and by comparison of this model with a previously described allometric centered model. It is shown that the network model is superior to the centered model in three ways: (1) The allometric network model permits growth prediction when allometric constants are known; (2) the network model has significantly smaller errors than the centered model; and (3) the network model is capable of displaying growth kinematics of both the neural and facial skulls while in time there are marked transformations, such as relative rotations of two sets of cranial anatomic points.

Adolescent↗
PubMed1984

Constitutive equations of erythrocyte membrane incorporating evolving preferred configuration.

The erythrocyte membrane is modeled as a two-dimensional viscoelastic continuum that evolves under the application of stress. The present analysis of the erythrocyte membrane is motivated by the recent development of knowledge about its molecular structure. The constitutive equations proposed in the present analysis explain in a consistent manner the data on both the deformation and recovery phases of the micropipette experiment. The rheological equations of the present study are applied in a later section to the analysis of a plane membrane deformation that is quantitatively similar to the tank-treading motion of the erythrocytes in a shear field. The computations yield useful information on how the membrane viscosity becomes a more dominant feature in tank-treading motion. The material constants appearing in the proposed constitutive equations may be useful indications of the biochemical state of the membrane in health and disease.

Elasticity↗
PubMed1984

Continuum mechanical model of leukocytes during protopod formation.

A new continuum mechanical theory for protopod extension in leukocytes is developed. Protopod formation is an active process which is the basis for amoeboid displacement on substrates. Leukocytes may form protopods both when adhering to a substrate and when freely suspended in plasma. Therefore the required energy is derived from the cell itself. Protopods are depleted of granules and other organelles, they have a fine fibrillar ultrastructure, and they are covered by a cell membrane. They grow at about 5 micron/min until they reach a length of 4-5 micron. A period of protopod retraction follows during which granules re-enter via the protopod base by Brownian motion. Micropipette experiments have indicated that the protoplasm in the leukocyte has viscoelastic properties, whereas the protopod is stiffer and shows elastic behavior. We propose a continuum theory based on the polymerization of the actin matrix in the cell which results in gelation with a preferred orientation. It is triggered by influx of Ca++ across local regions of the cell membrane and the polymerization occurs along an interface at the base of the polymerized protopod. As cytoplasm passes through the interface it is subject both to a volumetric strain due to exclusion of granules and a shear strain due to alignment of actin molecules. The polymerization provides an active force leading to projection of the protopod and cell deformation. The base of the protopod rests on the unpolymerized cytoplasm along the interface. As the external plasma medium and the cell membrane, if it is not stretched taut, offer little resistance, the projection of the protopod proceeds outward with simultaneous unfolding of the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1984

Hydrodynamic and mechanical aspects of endothelial permeability.

The passive transport of water through the endothelial cell layer junctions is considered from the standpoint of hydrodynamic theories based on ultrastructural information. The local geometry of tight junctions based on molecular level forces and elastic membrane properties has been modeled and leads to estimates of the hydraulic resistance of the clefts. It is shown that the large resistance measured experimentally can be accounted for in this model. The transport of large macromolecules via vesicles which diffuse across the endothelial cell has been developed, but recent experimental data do not appear to support this mechanism as a primary pathway. Fused vesicles forming an open channel appear to be rare. Leaky junctions, such as around dying endothelial cells or produced by cytoskeletal changes within the cells, may be important in control of endothelial permeability. Another kind of model is a fiber matrix model of the endocapillary layer, extending into the intercellular clefts which can also account for the molecular seiving properties of the endothelial cell layer but may produce a large resistance to water flux.

Biological Transport↗
PubMed1984

Aggregation and disaggregation of red blood cells.

The aggregation of red blood cells may be analyzed as an interaction of an adhesive surface energy and the elastic stored energy which results from deformation of the cell. The adhesive surface energy is the work required to separate a unit adhered area and is the resultant of adhesive forces due to the bridging molecules that bind the cells together and the electrostatic repulsion due to surface charge. The elastic strain energy in the case of the red blood is associated with the membrane elasticity only since the interior of the cell is liquid. The membrane elasticity is due both to bending stiffness and shear. The area expansion is small and may be neglected. These assumptions allow realistic computation of red cell shapes in rouleaux. The disaggregation of rouleaux requires an external force which must overcome the adhesive energy and also supply additional elastic energy of deformation. Depending on the geometry, the initial effect of elastic energy may tend to aid disaggregation. In a shear flow, the stresses on a suspended rouleau alternately tend to compress and to disaggregate the cells if they are free to rotate. This introduces a time dependence so that viscous effects due to the viscosity of the cell membrane, the cell cytoplasm and the external fluid may play a role in determining whether disaggregation proceeds to completion or not.

Blood Viscosity↗
PubMed1984

Deformation of leukocytes on a hematological blood film.

Human leukocytes in a blood film exhibit a significantly larger diameter than in the circulation. This is due to the fact that white cells are highly deformed during preparation of a blood film. Instead of having the usual spherical shape, the cells are compressed to "pancake" forms with a thickness of about 1 micron. Hematological investigation is usually performed on these compressed cells, but in the circulation they are not observed. The deformation of the cells on a blood film is due to compression by the glass edge used to spread the blood. After deformation leukocytes do not have enough time to recover since the blood film usually dries in a shorter period than is needed for cell recovery. The shape and size of the leukocyte on the blood film is not only determined by cell volume but also by the cell membrane area. This is shown for each kind of leukocyte by independent prediction of the pancake dimensions from previous measurements of cell volume and membrane area. Leukocytes which are strongly compressed during blood film preparation may exhibit mechanical damage with rupture of membranes.

Blood Specimen Collection↗
PubMed1984

Viscoelastic properties of leukocytes.

The viscoelastic properties of leukocytes (WBCs) during small deformation were determined by micropipette aspiration. The passive deformation behavior of neutrophils suspended in a Ca2+-free medium in response to a step aspiration pressure consists of an initial rapid, elastic response followed by a creep displacement. These time-dependent responses can be modeled by a viscoelastic solid in which an elastic element (K1) is in parallel with a Maxwell element composed of another elastic element (K2) in series with a viscous element (mu). Variations in temperature (9-40 degrees C) cause an inverse change in mu, but have no effects on K1 and K2. All three coefficients are not affected by decreases in pH down to 5.4; with pH greater than or equal to 7.8, however, K1 and mu increase. Increases in osmolality cause a rise in all three coefficients, especially mu. Colchicine treatment results in selective decreases in mu and K2 without affecting K1. B lymphocytes have viscoelastic coefficients similar to those of neutrophils, but T lymphocytes have higher values for these coefficients. In the presence of 2 mM Ca2+, the neutrophils have higher viscoelastic coefficients than in Ca2+-free medium, and they form protopods which have greater resistance than the main cell body to deformation by micropipette aspiration. Morphometric analysis shows that WBCs have large excess membrane area due to the presence of membrane foldings, which facilitate WBC deformation at constant area. During filtration through 5-micrometers sieves, WBCs are much more prone to pore plugging than erythrocytes because of their higher cellular viscosity and the presence of nucleus. The rheological properties of WBCs have significant implications in their functions and flow dynamics in the microcirculation.

Colchicine↗
PubMed1983

Steady-state analysis and evaluation of a new thermal sensor for surface measurements of tissue perfusion.

The steady-state response and operating characteristics of a new thermal sensor for surface measurements of local tissue perfusion have been analyzed theoretically and evaluated in vivo. The flow measurement system incorporates an electrically isolated thin-film thermal sensor, which is maintained at a fixed temperature by high frequency response electronic circuitry. The sensor rests on the tissue surface, and the power required to maintain a fixed probe to tissue temperature elevation is measured and related to tissue blood flow. A theoretical analysis of the steady-state probe response to flow changes was carried out employing the bio-heat-transfer equation and a solution based on Fourier series to describe the temperature distribution within the tissue domain. A comparison of steady-state theory to results obtained from initial experimental tests on the surface of the dog heart, over a perfusion range 0.51 to 2,00 ml/min/g, shows close agreement. The probe demonstrates good sensitivity to flow changes, provides stable and continuous measurements, and appears promising for both research and clinical applications.

Animals↗
PubMed1983

Statistical testing of an allometric centered model of craniofacial growth.

An allometric centered model of craniofacial growth was tested by several computer-assisted statistical methods on the pure longitudinal growth data of twenty-four close-bred female rats and on cross-sectional human cranial growth data. The study demonstrated that such a model was heuristic and, being incapable of exact definition, was deemed inappropriate for further use in modeling of craniofacial skeletal growth. The necessity for vigorous testing of any hypothesis concerning the modeling of craniofacial growth is stressed.

Adolescent↗
PubMed1983

Biomechanical considerations in osseointegrated prostheses.

On the basis of the previous discussions, several conclusions may be drawn. 1. The close apposition of bone to the titanium implant is the essential feature that allows a transmission of stress from the implant to the bone without any appreciable relative motion or abrasion. The absence of any intermediate fibrotic layer allows stress to be transmitted without any progressive change in the bond or contact between the bone and implant. 2. The use of a threaded screw provides a form of interlocking with the bone on a macroscopic scale that allows full development of the strength of the bone in shear or compression. A smooth, cylindrical implant may require an adhesive bond for satisfactory performance, but a screw shape is able to work as long as the apposition of bone and implant is close, whether or not a true adhesive bond is developed. 3. The distribution of a vertical or lateral load applied to a fixed partial denture depends on the number, arrangement, and stiffness of abutment fixtures used, as well as the form and stiffness of the fixed prosthesis itself. In general a stiff fixed partial denture will distribute loads to several fixtures more effectively. A flexible prosthesis may be adequate if the strength developed by each fixture is able to carry the full load that is applied. Cantilevered ends of a fixed partial denture increases the loading on the first screw nearest the cantilevered end. Moderate overhangs may be tolerated if the fixtures are sufficiently strong. 4. A tight connection of the fixed partial denture to fixtures provides a combined structure that can act in concert with the bone to provide a greater strength than that of the fixture or the jaw bone alone. 5. The osseointegrated implant provides a direct contact with bone and therefore will transmit any stress waves or shocks applied to the fixtures. For this reason it is advisable to use a shock-absorbing material such as acrylic resin in the form of acrylic resin artificial teeth in the fixed partial denture. This arrangement allows for the development of a stiff and strong substructure with adequate shock protection on its outer surface.

Bone Screws↗
PubMed1983

Theoretical models of rouleau formation and disaggregation.

The formation of rouleaux of red blood cells is considered as an interaction of the surface adhesive energy and the elastic strain energy of the red blood cell membrane. A dynamic energy equation is written which applies to both the process of aggregation and the disaggregation by external forces. Any equilibrium state may be regarded as minimization of the appropriate energy potentials. The theory is illustrated by the computation of the shapes of two cell rouleaux under different surface adhesive energies. Disaggregation is studied in a model in which the red blood cells are idealized as cylindrical forms. It is shown that during disaggregation the strain energy stored in the cell contributes to the work done in overcoming the adhesive energy.

Cell Adhesion↗
PubMed1983

Energy balance in red cell interactions.

Experiments were performed to elucidate the balance of energies involved in the formation of red blood cell (RBC) aggregates and in their disaggregation. In order to achieve a mean stable rouleau formation, the aggregating energy provided by macromolecular binding to the cell membrane must overcome the disaggregation energy of electrostatic repulsion between RBC surfaces and the effects of mechanical shear stress. In a quiescent suspension the net aggregation energy is largely stored in the membrane as a change in strain energy. The alterations in strain energy cause the curvature of the end cells in rouleaux of normal RBCs in Dx 80 to change from concave to convex and back again to concave as [Dx 80] was increased from 1 to 4 to 6 g/dl; computation of net aggregation energy per unit area (gamma) from changes in membrane strain energy yielded values on the order of 10(3) ergs/cm2. The end cells of neuraminidase-treated RBCs remained convex with [Dx 80] above 2 g/dl, and gamma is probably on the order of 10(2) ergs/cm2. The variations in gamma with [Dx 80] and RBC surface charge are similar to variations in reflectometric aggregation index without shear ( RAI0 ), indicating that RAI0 reflects gamma. The difference in gamma between normal and neuraminidase-treated RBCs represents the electrostatic repulsive energy, the magnitude of which varied inversely with dextran molecular size and directly with [Dx]. Moderate shearing in the reflectometer enhanced RBC aggregation by promoting cell-cell encounter, but high shear stresses cause RBC disaggregation. The energy required to disaggregate a unit interacting area of normal RBCs in Dx 80 in a flow channel is on the order of 10(4) ergs/cm2, which is much lower than gamma. These results suggest that the release of the stored membrane strain energy during disaggregation aids in the separation process. The results show that the understanding of RBC aggregation requires the considerations of surface charge, properties of aggregating agents, and the rheology of the cell membrane.

Dextrans↗
PubMed1983

A new thermal sensor for surface-based measurement of local myocardial perfusion.

The transient response of a new thermal sensor for continuous surface-based measurement of local tissue blood flow was evaluated in the beating dog heart. The sensor is 2.5 mm square, tests on the heart, and responds to flow changes only within a region of tissue 3-4 mm below its location on the epicardial surface. Initial studies demonstrate excellent sensitivity, good frequency response with a time constant of the order of 10-11 s, and an ability to continuously monitor changes in local myocardial blood flow during a variety of well-understood interventions, including coronary artery occlusion, reactive hyperemia, and intravenous administration of nitroglycerin and dipyridamole.

Animals↗
PubMed1983

Role of white blood cells in filtration of blood cell suspensions.

The time-dependent filtration pressure curves of cell suspensions pumped through 5 microns polycarbonate filters at a constant flow rate were analyzed with the aid of a theoretical model developed in an accompanying paper. The cell suspensions contained mixtures of erythrocytes and leukocytes, the concentrations of which were systematically varied. The pressure-time (P-t) curves generally showed multiphasic components. Following the attainment of a quasi-steady state level, the pressure rose first rapidly and then more slowly. The rates of pressure rise in the fast and slow phases were normalized by using the steady state pressure reading (PO) obtained with Ringer solution at the same flow rate, and are designated k1 and k2, respectively. Both k1 and k2 increased with rising concentrations of leukocytes, [WBC], or erythrocytes, [RBC]. [WBC] is 700-1000 times more effective than [RBC] in affecting k1 and k2. k1 is related to the dynamic plugging and unplugging of filter pores, primarily by leukocytes. k2 is attributable to the "permanent" plugging of filter pores, again predominantly by leukocytes. The experimental P-t curves can be fitted with the theoretical model by using appropriate constants for leukocyte plugging. The results indicate that nearly 2/3 of the entering leukocytes cause transient plugging of pores, with an unplugging rate of 4.1 percent/sec/unit pressure rise, and that approximately 2.2 percent of the entering leukocytes are "permanently" lodged. These results underscore the important role of leukocytes in determining the later phase of the P-t curve and support the concept that leukocyte plugging may have pathophysiological significance in causing microvascular occlusion in disease states.

Erythrocytes↗
PubMed1983

Influence of red cell concentration on filtration of blood cell suspensions.

Pressure-time curves obtained by passing suspensions of blood cells in Ringer solution through a 5 microns polycarbonate filter at constant flow (1.6 ml/min) were evaluated for their ability to reflect the deformability of the erythrocytes. The initial pressure reading (Pi) obtained in a quasi-steady state during the first 1-2 sec of pumping was found to be reproducible for hematocrit values between 10 and 30 percent. This Pi value was normalized by the pressure generated by the cell-free suspending medium (PO) at the same flow rate. The ratio Pi/PO was found to be linearly proportional to hematocrit up to 30 percent but independent of leukocyte concentration up to 12,000/mm3. Later portions of the curve did vary with leukocyte count. By using the equations developed from theoretical modeling of cells passing through a filter, the experimentally determined relation of Pi/PO to hematocrit, and the known geometry of the filter pores, we were able to calculate parameters reflecting the deformability of red cells. These include beta, the ratio of resistance in a pore containing a red cell to that in a pore containing only the suspending medium, and alpha, the proportion of pores filled by erythrocytes in transit. The application of theoretical analysis to experimental data has provided quantitative insights into the behavior of red cells during filtration tests in normal and disease states.

Erythrocytes↗