Loading-Induced Interstitial Fluid Flow in Bone Mechanobiology: An FSI Approach to the Osteocyte Environment

2012 ◽  
Author(s):  
Stefaan W. Verbruggen ◽  
Ted J. Vaughan ◽  
Laoise M. McNamara
Keyword(s):  
Adaptive Response ◽  
Interstitial Fluid ◽  
Bone Growth ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Physiological Demands ◽  
Control Bone ◽  
Ubiquitous Presence

Bone is an adaptive material, which is particularly responsive to mechanical loading and can adapt its mass and structure to meet the mechanical demands experienced throughout life. The osteocyte, due to its ubiquitous presence throughout bone, is believed to act as the main sensor of mechanical stimulus in bone, recruiting other cells to control bone growth and resorption in response to changes in physiological demands. However the precise mechanical stimuli that osteocytes experience in vivo, and what type of stimulus instigates an adaptive response, are not fully understood.

Fluid-Structure Interaction Modelling Predicts That Strain Transfer Through Focal Attachments of Osteoblast Cells are the Primary Mediators of Mechanical Stimulation Under Fluid Flow

2013 ◽  
Author(s):  
T. J. Vaughan ◽  
M. G. Haugh ◽  
L. M. McNamara
Keyword(s):  
Fluid Flow ◽  
Mechanical Stimulation ◽  
Interstitial Fluid ◽  
Bone Cells ◽  
Mechanical Stimulus ◽  
Mechanical Stimuli ◽  
Interstitial Fluid Flow ◽  
Interaction Modelling

Bone continuously adapts its internal structure to accommodate the functional demands of its mechanical environment. It has been proposed that indirect strain-induced flow of interstitial fluid surrounding bone cells may be the primary mediator of mechanical stimuli in-vivo [1]. Due to the practical difficulties in ascertaining whether interstitial fluid flow is indeed the primary mediator of mechanical stimuli in the in vivo environment, much of the evidence supporting this theory has been established through in vitro investigations that have observed cellular activity in response to fluid flow imposed by perfusion chambers [2]. While such in vitro experiments have identified key mechanisms involved in the mechanotransduction process, the exact mechanical stimulus being imparted to cells within a monolayer is unknown [3]. Furthermoreit is not clear whether the mechanical stimulation is comparable between different experimental systems or, more importantly, is representative of physiological loading conditions experienced by bone cells in vivo.

scholarly journals Strain amplification in bone mechanobiology: a computational investigation of the in vivo mechanics of osteocytes

2012 ◽  
Vol 9 (75) ◽  
pp. 2735-2744 ◽  
Author(s):  
Stefaan W. Verbruggen ◽  
Ted J. Vaughan ◽  
Laoise M. McNamara
Keyword(s):  
Computational Models ◽  
Bone Growth ◽  
Bone Cells ◽  
Physiological Activity ◽  
Three Dimensional ◽  
Mechanical Stimulus ◽  
Confocal Imaging ◽  
Mechanical Stimuli ◽  
Confocal Image

The osteocyte is believed to act as the main sensor of mechanical stimulus in bone, controlling signalling for bone growth and resorption in response to changes in the mechanical demands placed on our bones throughout life. However, the precise mechanical stimuli that bone cells experience in vivo are not yet fully understood. The objective of this study is to use computational methods to predict the loading conditions experienced by osteocytes during normal physiological activities. Confocal imaging of the lacunar–canalicular network was used to develop three-dimensional finite element models of osteocytes, including their cell body, and the surrounding pericellular matrix (PCM) and extracellular matrix (ECM). We investigated the role of the PCM and ECM projections for amplifying mechanical stimulation to the cells. At loading levels, representing vigorous physiological activity (3000 µ ɛ ), our results provide direct evidence that (i) confocal image-derived models predict 350–400% greater strain amplification experienced by osteocytes compared with an idealized cell, (ii) the PCM increases the cell volume stimulated more than 3500 µ ɛ by 4–10% and (iii) ECM projections amplify strain to the cell by approximately 50–420%. These are the first confocal image-derived computational models to predict osteocyte strain in vivo and provide an insight into the mechanobiology of the osteocyte.

scholarly journals Mechanosensitive recruitment of stator units promotes binding of the response regulator CheY-P to the flagellar motor

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jyot D. Antani ◽  
Rachit Gupta ◽  
Annie H. Lee ◽  
Kathy Y. Rhee ◽  
Michael D. Manson ◽  
...  
Keyword(s):  
Adaptive Response ◽  
Mechanical Load ◽  
Response Regulator ◽  
Mechanical Stimulus ◽  
Viscous Resistance ◽  
Mechanical Forces ◽  
Mechanical Stimuli ◽  
Flagellar Motor ◽  
Neuromuscular Systems ◽  
Bacterial Flagellar Motor

AbstractReversible switching of the bacterial flagellar motor between clockwise (CW) and counterclockwise (CCW) rotation is necessary for chemotaxis, which enables cells to swim towards favorable chemical habitats. Increase in the viscous resistance to the rotation of the motor (mechanical load) inhibits switching. However, cells must maintain homeostasis in switching to navigate within environments of different viscosities. The mechanism by which the cell maintains optimal chemotactic function under varying loads is not understood. Here, we show that the flagellar motor allosterically controls the binding affinity of the chemotaxis response regulator, CheY-P, to the flagellar switch complex by modulating the mechanical forces acting on the rotor. Mechanosensitive CheY-P binding compensates for the load-induced loss of switching by precisely adapting the switch response to a mechanical stimulus. The interplay between mechanical forces and CheY-P binding tunes the chemotactic function to match the load. This adaptive response of the chemotaxis output to mechanical stimuli resembles the proprioceptive feedback in the neuromuscular systems of insects and vertebrates.

Direct Hydraulic Permeability Measurements of Agarose Hydrogels Used as Cell Scaffolds

1999 ◽  
Author(s):  
Michael A. Soltz ◽  
Anna Stankiewicz ◽  
Gerard Ateshian ◽  
Robert L. Mauck ◽  
Clark T. Hung
Keyword(s):  
Fluid Flow ◽  
Articular Cartilage ◽  
Interstitial Fluid ◽  
Convective Transport ◽  
Hydraulic Permeability ◽  
Interstitial Fluid Flow ◽  
Pass Through ◽  
Fluid Pressurization ◽  
First Time

Abstract The objective of this study was to determine the intrinsic hydraulic permeability of 2% agarose hydrogels. Two-percent agarose was chosen because it is a concentration typically used for encapsulation of chondrocytes in suspension cultures [3–5], Hydraulic permeability is a measure of the relative ease by which fluid can pass through a material. Importantly, it governs the level of interstitial fluid flow as well as the interstitial fluid pressurization that is generated in a material during loading. Fluid pressurization is the source of the unique load-bearing and lubrication properties of articular cartilage [1,17] and represents a major component of the in vivo chondrocyte environment. We have previously reported that 2% agarose hydrogels can support fluid pressurization, albeit to a significantly lesser degree than articular cartilage [18]. Interstitial fluid flow gives rise to convective transport of nutrients and ions [6,7] and matrix compaction [9] which may serve as important stimuli to chondrocytes. We report for the first time the strain-dependent hydraulic permeability of 2% agarose hydrogels.

scholarly journals Microvasculature-on-a-Chip: Bridging the interstitial blood-lymph interface via mechanobiological stimuli

2021 ◽  
Author(s):  
Barbara Bachmann ◽  
Sarah Spitz ◽  
Christian Jordan ◽  
Patrick Schuller ◽  
Heinz D Wanzenboeck ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Fluid Flow ◽  
Interstitial Fluid ◽  
Lymphatic System ◽  
Immune Cell ◽  
Scientific Progress ◽  
Morphological Characteristics ◽  
Interstitial Fluid Flow

After decades of simply being referred to as the body's sewage system, the lymphatic system has recently been recognized as a key player in numerous physiological and pathological processes. As an essential site of immune cell interactions, the lymphatic system is a potential target for next-generation drug delivery approaches in treatments for cancer, infections, and inflammatory diseases. However, the lack of cell-based assays capable of recapitulating the required biological complexity combined with unreliable in vivo animal models currently hamper scientific progress in lymph-targeted drug delivery. To gain more in-depth insight into the blood-lymph interface, we established an advanced chip-based microvascular model to study mechanical stimulation's importance on lymphatic sprout formation. Our microvascular model's key feature is the co-cultivation of spatially separated 3D blood and lymphatic vessels under controlled, unidirectional interstitial fluid flow while allowing signaling molecule exchange similar to the in vivo situation. We demonstrate that our microphysiological model recreates biomimetic interstitial fluid flow, mimicking the route of fluid in vivo, where shear stress within blood vessels pushes fluid into the interstitial space, which is subsequently transported to the nearby lymphatic capillaries. Results of our cell culture optimization study clearly show an increased vessel sprouting number, length, and morphological characteristics under dynamic cultivation conditions and physiological relevant mechanobiological stimulation. For the first time, a microvascular on-chip system incorporating microcapillaries of both blood and lymphatic origin in vitro recapitulates the interstitial blood-lymph interface.

Anabolic Fluid Flow as Dependent on It Dose and Frequency in Bone Formation and Inhibition of Bone Loss

2004 ◽  
Author(s):  
Yi-Xian Qin ◽  
Tamara Kaplan ◽  
Hoyan Lam
Keyword(s):  
Fluid Flow ◽  
Adaptive Response ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Bone Adaptation ◽  
Fluid Loading ◽  
Interstitial Fluid Flow ◽  
Flow Rates ◽  
Dynamic Components ◽  
One Year

Anabolic response of bone to interstitial fluid flow is strongly dependent on the dynamic components of the fluid pressure, implying that fluid flow is a critical regulatory component to bone mass and morphology. While the fluid stimulus can be potentially applied for therapeutic in promoting turnover, the hypothesis of fluid induced bone adaptation was evaluated in an avian ulna model using varied flow rates and magnitudes. Total of 12 one-year old male avian animals was used in this study. A sinusoidal fluid pressure was applied to the experimental ulna 10 min/day for 4 weeks. Three experimental groups of loading were performed at 1 and 30 Hz of fluid loading. The results reveal an increase of 22.7%±7.2 in trabecular volume for group of 30 Hz, 76mmHg loading, while it had only 0.5 % increase at 1Hz, 76 mmHg loading. Under physiologic fluid pressure, a higher flow rate of stimuli generates much higher remodeling response than a lower rate of loading. This implies that bone turnover may be sensitive to the dynamic components of fluid flow, thereby initiating the adaptive response.

scholarly journals The Mechanical Microenvironment in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1452
Author(s):  
Stephen J.P. Pratt ◽  
Rachel M. Lee ◽  
Stuart S. Martin
Keyword(s):  
Breast Cancer ◽  
Interstitial Fluid ◽  
Fluid Pressure ◽  
Normal Breast ◽  
Interstitial Fluid Pressure ◽  
Mechanical Stimuli ◽  
Solid Stress ◽  
Physical Cues

Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.

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