Phospholipid Morphologies on Photochemically Patterned Silane Monolayers

Howland, Michael C.; Sapuri-Butti, Annapoorna R.; Dixit, Sanhita; Dattelbaum, Andrew M.; Shreve, and Andrew P.; Parikh, Atul N.

doi:10.1021/ja043439q

Cited by 85 publications

(151 citation statements)

References 66 publications

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“…Three rate equations were incorporated into the simulation: (i) production of C at the surface of the patch, rate ϭ k patch, ; (ii) autocatalytic production of C in solution, rate ϭ k prod [C] 2 ϩ b; and (iii) linear consumption of C in solution, rate ϭ Ϫk consum [C]. The values used were Patterned substrates were prepared by using photolithography (26,32). Glass coverslips were extensively cleaned and then made inert to clotting, either by forming a bilayer of phosphatidylcholine or a monolayer of hydrophobic silanes.…”

Section: Methodsmentioning

confidence: 99%

“…To initiate this pathway, we exposed blood plasma to negatively charged glass, and initiation occurred in t R ϳ 9 min. We used the diffusion coefficient for thrombin to predict the threshold patch size p tr ϳ (D ϫ t R ) 1/2 ϳ 160 m. To test this prediction, we created patches of hydrophilic glass in a background of inert, hydrophobic silanized glass (32). We rapidly determined p tr ϳ 100 m by placing blood plasma on a single array of patches of different sizes (Fig.…”

Section: Initiation Of Clotting In the Chemicalmentioning

confidence: 99%

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Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Kastrup

Runyon

Shen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

103

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This article demonstrates that a simple chemical model system, built by using a modular approach, may be used to predict the spatiotemporal dynamics of initiation of blood clotting in the complex network of hemostasis. Microfluidics was used to create in vitro environments that expose both the complex network and the model system to surfaces patterned with patches presenting clotting stimuli. Both systems displayed a threshold response, with clotting initiating only on isolated patches larger than a threshold size. The magnitude of the threshold patch size for both systems was described by the Damkö hler number, measuring competition of reaction and diffusion. Reaction produces activators at the patch, and diffusion removes activators from the patch. The chemical model made additional predictions that were validated experimentally with human blood plasma. These experiments show that blood can be exposed to significant amounts of clot-inducing stimuli, such as tissue factor, without initiating clotting. Overall, these results demonstrate that such chemical model systems, implemented with microfluidics, may be used to predict spatiotemporal dynamics of complex biochemical networks.complexity ͉ microfluidics ͉ networks ͉ tissue factor ͉ nonlinear

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Section: Methodsmentioning

confidence: 99%

Section: Initiation Of Clotting In the Chemicalmentioning

confidence: 99%

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Kastrup

Runyon

Shen

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

103

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“…6,28 A monolayer of neutral phospholipid, 1,2-Dilauroyl-sn-glycero-3-phosphocholine (DLPC), was formed in silanized silica capillaries. Portions of this lipid and silane surface were selectively removed by deep-UV photolithography.…”

Section: Patterning Inert Silica Capillaries With Patches Of Tfmentioning

confidence: 99%

Threshold Response of Initiation of Blood Coagulation by Tissue Factor in Patterned Microfluidic Capillaries Is Controlled by Shear Rate

Shen

Kastrup

Liu

et al. 2008

ATVB

111

115

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Objective-Blood flow is considered one of the important parameters that contribute to venous thrombosis. We quantitatively test the relationship between initiation of coagulation and shear rate and suggest a biophysical mechanism to understand this relationship. Methods and Results-Flowing human blood and plasma were exposed to cylindrical surfaces patterned with patches of tissue factor (TF) by using microfluidics. Initiation of coagulation of normal pooled plasma depended on shear rate, not volumetric flow rate or flow velocity, and coagulation initiated only at shear rates below a critical value. Initiation of coagulation of platelet-rich plasma and whole blood showed similar behavior. At constant shear rate, coagulation of plasma also showed a threshold response to the size of a patch of TF, consistent with our previous work in the absence of flow. Conclusion-Initiation of coagulation of flowing blood displays a threshold response to shear rate and to the size of a surface patch of TF. Combined with the results of others, these results set the range of shear rates that limit initiation of coagulation by small surface areas of TF and by shear activation of platelets. This range fits the relatively narrow range of physiological shear rates described by Murray's law. T his article analyzes initiation of coagulation of blood flowing over a patch presenting tissue factor (TF) in the regime where platelets are not activated by shear alone. TF is the primary stimulus for initiation of coagulation in vivo. [1][2][3] We demonstrate that initiation of coagulation displays a threshold response to shear rate and to the size of the patch of TF, and we suggest a biophysical mechanism that explains these threshold phenomena. While low blood flow and endothelial damage are known risk factors for coagulation, 4 the precise effects of blood flow on the initiation of coagulation are not fully characterized, possibly because of the difficulty in experimentally decoupling the effects of volumetric flow rate, flow velocity, and shear rate.The effects of flow and shear rate on the activation of coagulation factors have been studied previously, 5-12 but whether high or low shear rates promote initiation of coagulation remains unclear. Intuitively, high blood flow and shear rates may promote coagulation by increasing the rate of delivery of coagulation proenzymes to sites of vascular damage. Indeed, high shear rates have been shown to increase the generation of factor Xa from surfaces coated with the TF and factor VIIa complex (TF-VIIa). 11 Moreover, high shear rates increase the potential for shear activation of platelets. 13,14 On the other hand, numeric simulations have predicted that low blood flow could promote initiation by reducing the removal of activated coagulation factors from surfaces of TF-VIIa, 15 and, clinically, stasis and low blood flow are considered risk factors for deep vein thrombosis (DVT). 16 Low shear rates have also been found to increase fibrin deposition and appearance of fibrin monomers, indicating that l...

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“…The impact of such deformations on lipid partitioning and mobility are not well understood, particularly in the context of a substrate-supported lipid bilayer interfacing with a material barrier. Notably, previous studies have provided mixed results into even the spatial influence of such an edge region on diffusion, ranging from sub-micrometer to multimicrometer distances [23][24][25][26] ; in particular, Howland and colleagues 26 identified a non-fluid phase and lipid-free moat in fluid bilayers surrounding a change in surface chemistry.Assuming a similar, dramatic change in diffusivity, namely that of a non-fluid boundary region at the bilayer-barrier interface, our observations of diffusion parallel to the barriers suggests that any such boundary layer must be much less than half of the distance between the smallest barrier spacing, thus less than 33-nm. Furthermore, the good agreement between our experimental measurements and the continuum model suggest that in the assumption of a nonfluid boundary layer, such a region must be small compared to the smallest gap spacing (30 nm), or on the order of 10s of nanometers.…”

mentioning

confidence: 99%

Non-Brownian Diffusion of Membrane Molecules in Nanopatterned Supported Lipid Bilayers

et al. 2008

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Molecules associated with the outer surface of living cells exhibit complex, non-Brownian patterns of diffusion. In this report, supported lipid bilayers were patterned with nanoscale barriers to capture key aspects of this anomalous diffusion in a controllable format. First, long-range diffusion coefficients of membrane-associated molecules were significantly reduced by the presence of the barriers, while short-range diffusion was unaffected. Second, this modulation was more pronounced for large molecular complexes than for individual lipids. Surprisingly, the quantitative effect of these barriers on long-range lipid diffusion could be accurately simulated using a simple, continuum-based model of diffusion on a nanostructured surface; we thus describe a metamaterial that captures the properties of the outer membrane of living cells.The outer surface of cells presents a complex, nanostructured, yet fluid environment that controls the movement of signaling proteins. The lateral movement of many membrane biomolecules, including transmembrane or tethered proteins as well as lipids themselves, can be interpreted as being free and isotropic within compartments of the cell membrane measuring tens to hundreds of nanometers in scale [1][2][3][4][5][6] . These compartments are delineated by semipermeable barriers that arise from interactions between the plasma membrane, underlying cytoskeleton, and associated proteins [6][7][8] . Fluctuations in these structures allow biomolecules to occasionally cross between compartments, allowing long-range, but comparatively slow, transport over the cell surface. More formally, transport along the membrane is an anomalous, non-Brownian process that can be characterized by two diffusion coefficients, one that describes short-range motion within an individual compartment and a second, smaller, effective diffusion coefficient that is associated with long-range motion over many barriers. The extent to which these values differ is dependent on the spacing and properties of the barriers as well as the diffusing molecule. Emerging models suggest significant impacts of this behavior on cell signaling 2, 9, 10 , but experimental systems for testing these hypotheses are not widely available. In this report, we capture this anomalous diffusion by nanopatterning supported lipid bilayers with barriers to lipid diffusion using a geometry that captures the semipermeable nature of those posed to be present in living cells. As is posed by models of these interactions, we aim to gain control over long-range diffusion, while maintaining local, isotropic diffusion associated with a membrane in the absence of such barriers. We demonstrate that these nanopatterned barriers give rise to different short-and long-range diffusion coefficients of lipids and membrane-associated proteins, and provide a quantitative model of this diffusion that suggests specific aspects of membrane structure at the sub-micrometer level. The basic substrate supported lipid bilayer system consists of a phospholipid membrane...

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Phospholipid Morphologies on Photochemically Patterned Silane Monolayers

Cited by 85 publications

References 66 publications

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Modular chemical mechanism predicts spatiotemporal dynamics of initiation in the complex network of hemostasis

Threshold Response of Initiation of Blood Coagulation by Tissue Factor in Patterned Microfluidic Capillaries Is Controlled by Shear Rate

Non-Brownian Diffusion of Membrane Molecules in Nanopatterned Supported Lipid Bilayers

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