Dynamics of Interstitial Fluid Pressure in Extracellular Matrix Hydrogels in Microfluidic Devices

In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (∼100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure.

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Cytochalasin D induces edema formation and lowering of interstitial fluid pressure in rat dermis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.1.h7 ◽

2001 ◽

Vol 281 (1) ◽

pp. H7-H13 ◽

Cited By ~ 18

Author(s):

Ansgar Berg ◽

Kristofer Rubin ◽

Rolf K. Reed

Keyword(s):

Extracellular Matrix ◽

Interstitial Fluid ◽

Acute Inflammation ◽

Cultured Cells ◽

Circulatory Arrest ◽

Fluid Pressure ◽

Cytochalasin D ◽

Interstitial Fluid Pressure ◽

Edema Formation ◽

Fluid Filtration

The increased capillary fluid filtration required to create a rapid edema formation in acute inflammation can be generated by lowering the interstitial fluid pressure (PIF). The lowering of PIF appears to involve dynamic β1-integrin-mediated interactions between dermal cells and extracellular matrix fibers. The present study specifically investigates the role of the cell cytoskeleton, i.e., the contractile apparatus of cells, in controlling PIF in rat skin as the integrins are linked to both the cytoskeleton and the extracellular matrix. PIF was measured using a micropuncture technique in the dorsal skin of the hind paw at a depth of 0.2–0.5 mm and following the induction of circulatory arrest with the intravenous injection of KCl in pentobarbital anesthesia. This procedure prevented the transcapillary flux of fluid and protein leading to edema formation in acute inflammation, which in turn can increase the PIF and therefore potentially mask a decrease of PIF. Control PIF ( n = 42) averaged −0.8 ± 0.5 (means ± SD) mmHg. In the first group of experiments, subdermal injection of 2 μl cytochalasin D, a microfilament-disrupting drug, lowered PIF to an average of −2.8 ± 0.7 mmHg within 40 min postinjection ( P< 0.05 compared with control). Subdermal injection of vehicle (10% DMSO in PBS or PBS alone) did not change the PIF( P > 0.05). Lowering of the PIF was not observed after the injection of colchicine or nocodazole, which specifically disrupts microtubuli in cultured cells. In the second group of experiments, 2 μl of cytochalasin D injected subdermally into rats with intact circulation increased the total tissue water (TTW) and albumin extravasation rate ( E ALB) by 0.7 ± 0.2 and 0.4 ± 0.3 ml/g dry wt, respectively ( P < 0.05 compared with vehicle). Nocodazole and colchicine did not significantly alter the TTW or E ALB compared with the vehicle ( P > 0.05). Taken together, these findings strongly suggest that the connective tissue cells can participate in control of PIF via the actin filament system. In addition, the observation that subdermal injection of cytochalasin D lowered PIF indicates that a dynamic assembly and disassembly of actin filaments also occurs in the cells of dermal tissues in vivo.

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Transcapillary exchange: role and importance of the interstitial fluid pressure and the extracellular matrix

Cardiovascular Research ◽

10.1093/cvr/cvq143 ◽

2010 ◽

Vol 87 (2) ◽

pp. 211-217 ◽

Cited By ~ 94

Author(s):

Rolf K. Reed ◽

Kristofer Rubin

Keyword(s):

Extracellular Matrix ◽

Interstitial Fluid ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

Transcapillary Exchange

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Subcutaneous interstitial fluid pressure during external loading

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1981.240.5.r327 ◽

1981 ◽

Vol 240 (5) ◽

pp. R327-R329 ◽

Cited By ~ 3

Author(s):

N. P. Reddy ◽

V. Palmieri ◽

G. V. Cochran

Keyword(s):

Interstitial Fluid ◽

Cuff Pressure ◽

Applied Pressure ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

External Loading ◽

Decubitus Ulcers ◽

Normal Tissues ◽

Fibrous Network ◽

Yorkshire Pigs

Interstitial fluid pressure (IFP) distribution generated as a result of externally applied pressure (EAP) may play an important role in the etiology of decubitus ulcers. In the forelimbs of 10 thiopental sodium-anesthetized Yorkshire pigs, weighing 16-20 kg, we placed wick catheters 2-5 mm below the skin. After equilibration, we applied a pediatric cuff and added EAP. With zero EAP, the IFP was -3.9 +/- 1.4 (SD) mmHg. In each case of EAP, IFP as measured with the wick catheter increased and reached a plateau within 10-15 min. In normal tissues, IFP reached approximately 65-75% of EAP. When we created an edematous condition by preinfusing with excess saline, IFP was found to reach 100% of EAP. The total normal stress in the tissue, generated as a result of external cuff pressure, can be considered as a sum of interstitial fluid pressure and extranormal stress. Integrity of the fibrous network and pore fraction may be important in transmitting pressure to the fluid.

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Blood Volume and Interstitial Fluid Pressure in the Development and Reversal of Renal Hypertension in Rats

Clinical Science ◽

10.1042/cs059153s ◽

1980 ◽

Vol 59 (s6) ◽

pp. 153s-156s ◽

Cited By ~ 1

Author(s):

N. C. Trippodo ◽

L. P. Ziegler

Keyword(s):

Arterial Pressure ◽

Blood Volume ◽

Interstitial Fluid ◽

Renal Hypertension ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

Tissue Fluid ◽

Small Decrease ◽

Interstitial Pressure

1. During the development and maintenance of one-kidney, one-clip hypertension in rats, there were no significant differences in blood volume or interstitial fluid pressure compared with one-kidney control rats. 2. Rats with one-kidney, one-clip hypertension of 25 days' duration were either unclipped, sham-operated or nephrectomized. Over 24 h the changes in arterial pressure, blood volume and interstitial pressure in the sham and nephrectomized groups were insignificant. In the unclipped group arterial pressure decreased 50 mmHg to normal by 24 h and was associated with increased diuresis and a small decrease in blood volume (9.8%). Unclipped rats with the greatest urine outputs showed the largest decreases in interstitial pressure (r = 0.70, P<0.02). 3. Thus, in the reversal of this hypertension, changes in blood volume played only a partial role; decreased interstitial pressure was secondary to tissue fluid depletion from increased diuresis and normalization of arterial pressure required the presence of the unclipped kidney.

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