Geometric Determinants of Directional Cell Motility Revealed Using Microcontact Printing

Brock, Amy; Chang, Eric C.; Ho, Chia‐Chi; LeDuc, Philip; Jiang, Xingyu; Whitesides, George M.; Ingber, Donald E.

doi:10.1021/la026394k

Cited by 233 publications

(197 citation statements)

References 21 publications

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Section: The Effects Of Cspg Surface Concentrationmentioning

confidence: 97%

“…Ingber et al showed that cell bound surface area when controlled by micropatterning can have a profound effect on apoptosis [153] and provided new patterns to increase cell spread while diminishing cell substrate contacts with integrins [154]. Ingber also showed that lamellapodial extension direction and the orientation of tractional forces can be controlled through surface patterning [155,156].…”

Section: The Effects Of Cspg Surface Concentrationmentioning

confidence: 99%

“…Additionally, an understanding of the . Ingber also showed that lamellapodial extension direction and the orientation of tractional forces can be controlled through surface patterning [155,156].To explore the CSPG dose and time dependent integrin receptor upregulation response, we have developed a soft lithography stamp that allows the patterning of several distinct CSPG densities on a single substrate ( Figure 5) [120]. These, so-called "polka dot" patterns provided very interesting insight in growth cone pathfinding dynamics.…”

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confidence: 99%

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The effects of proteoglycan surface patterning on neuronal pathfinding

Hlady

Hodgkinson

2007

Materialwissenschaft Werkst

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Protein micropatterning techniques are increasingly applied in cell choice assays to investigate fundamental biological phenomena that contribute to the host response to implanted biomaterials, and to explore the effects of protein stability and biological activity on cell behavior for in vitro cell studies. In the area of neuronal regeneration the protein micropatterning and cell choice assays are used to improve our understanding of the mechanisms directing nervous system during development and regenerative failure in the central nervous system (CNS) wound healing environment. In these cell assays, protein micropatterns need to be characterized for protein stability, bioactivity, and spatial distribution and then correlated with observed mammalian cell behavior using appropriate model system for CNS development and repair. This review provides the background on protein micropatterning for cell choice assays and describes some novel patterns that were developed to interrogate neuronal adaptation to inhibitory signals encountered in CNS injuries. Rationale for studying the role of proteoglycans in CNS injuriesNeurons from the central nervous system (CNS) possess a limited capacity to regenerate beyond scar tissue formation barriers in injuries even in the presence of minimal trauma to tissue organization [1,2]. A major culprit in CNS neuronal regenerative failure are the inihibitory proteoglycans (PGs), which are upregulated at the site of CNS injuries. PGs are composed of a core protein with varying numbers of attached glycosaminoglycan (GAG) side chains [3,4]. Proteoglycans are first translated intracellularly into proteins in the endoplasmic reticulum, and then GAG chains are later attached in the Golgi apparatus before secretion into the extracellular space [5][6][7][8]. The study of PGs has particularly been pronounced in the field of neurobiology and development of the nervous system. Numerous studies have concluded that PGs act as barriers that direct the migration of neural crest cells and the outgrowth direction of pathfinding neurons during development [9][10][11][12][13][14][15][16][17]. A number of these studies have additionally shown that cell guidance by PGs is based on an inhibitory signal located within the chondroitin sulfate GAG chains [9,18,19], with the result that the artificial addition of chondroitin sulfate (CS) sugars to the developing nervous system disrupts normal pathfinding [20] as well as does the removal of chondroitin sulfate chains through enzymatic treatment [9,19]. Davies et al. found that chondroitin sulfate proteoglycans (CSPG) are a major constituent of the glial scar and that dorsal root ganglion (DRG) outgrowth termination coincided with an increase in CSPG expression density [21]. Other sources have also shown that CSPGs are upregulated after CNS injuries [22][23][24][25].Interestingly, native adult CNS neurons actually posses the intrinsic ability to regenerate when the wound healing environment is prepared by eliminating inhibitory factors [23,26,27]. In additi...

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Section: The Effects Of Cspg Surface Concentrationmentioning

confidence: 97%

Section: The Effects Of Cspg Surface Concentrationmentioning

confidence: 99%

mentioning

confidence: 99%

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The effects of proteoglycan surface patterning on neuronal pathfinding

Hlady

Hodgkinson

2007

Materialwissenschaft Werkst

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“…Micropatterning and surface engineering techniques are emerging as important tools to clarify the effects of microenvironment on cellular behavior by coordinating cell-surface, cell-cell and cell-culture medium interactions in a controlled manner [1][2][3][4], since the microenvironment is a defining factor in a wide range of cellular processes including proliferation, differentiation and expression of phenotype-specific functions. Particularly, in cell-based biosensors (CBBs) and tissue engineering, in vitro maintenance of well-differentiated primary cells as a tissue is necessary for long-term culture and monitoring of cells with specific functions.…”

Section: Introductionmentioning

confidence: 99%

Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

Otsuka

Nagamura

Kaneko

et al. 2012

Science and Technology of Advanced Materials

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A two-dimensional microarray of 10 000 (100 × 100) chondrocyte spheroids was constructed with a 100 µm spacing on a micropatterned gold electrode that was coated with poly(ethylene glycol) (PEG) hydrogels. The PEGylated surface as a cytophobic region was regulated by controlling the gel structure through photolithography. In this way, a PEG hydrogel was modulated enough to inhibit outgrowth of chondrocytes from a cell adhering region in the horizontal direction, which is critical for inducing formation of three-dimensional chondrocyte aggregations (spheroids) within 24 h. We further report noninvasive monitoring of the cellular functional change at the cell membrane using a chondrocyte-based field effect transistor. This measurement is based on detection of extracellular potential change induced as a result of the interaction between extracellular matrix protein secreted from spheroid and substrate at the cell membrane. The interface potential change at the cell membrane/gate interface can be monitored during the differentiation of spheroids without any labeling materials. Our measurements of the time evolution of the interface potential provide important information for understanding the uptake kinetics for cellular differentiation.

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“…4,6,7 In addition to engineering systems that achieve patterning of cells on surfaces, controlling the compliance of the underlying substrate is also important. While mechanical forces have long been known to play a critical role in cellular interactions with the extracellular matrix, particularly for adherent cells, [8][9][10][11][12] an appreciation of substrate stiffness as a significant factor in modulating cell behavior has only recently developed. 13 For example, recent work has demonstrated that myocytes sense differences between surfaces of varied elasticity, and express native phenotype only when exposed to substrates of stiffness typical of normal muscle.…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Interdigitated Micropatterns of Self-Assembled Polymer Nanofilms Containing Cell-Adhesive Materials

2006

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Micropatterns of different biomaterials with micro-and nanoscale features and defined spatial arrangement on a single substrate are useful tools for studying cellular-level interactions, and recent reports have highlighted the strong influence of scaffold compliance in determining cell behavior. In this paper, a simple yet versatile and precise patterning technique for the fabrication of interdigitated micropatterns of nanocomposite multilayer coatings on a single substrate is demonstrated through a combination of lithography and layer-by-layer (LbL) assembly processes, termed as Polymer Surface Micromachining (PSM). The first nanofilm pattern is constructed using lithography, followed by LbL multilayer assembly and lift-off, and the process is repeated with optical alignment to obtain interdigitated patterns on the same substrate. Thus, the method is analogous to surface micromachining, except that the deposition materials are polymers and biological materials that are used to produce multilayer nanocomposite structures. A key feature of the multilayers is the capability to tune properties such as stiffness by appropriate selection of materials, deposition conditions, and post-deposition treatments. Two-and four-component systems on glass coverslips are presented to demonstrate the versatility of the approach to construct preciselydefined, homogeneous nanofilm patterns. In addition, an example of a complex system used as a testbed for in vitro cell adhesion and growth is provided: micropatterns of poly(sodium 4-styrenesulfonate)/poly-L-lysine hydrobromide (PSS/PLL) and secreted phospholipase A 2 /poly (ethyleneimine) (PEI/sPLA 2 ) multilayers. The interdigitated square nanofilm array patterns were obtained on a single coverslip with poly(diallyldimethyl ammonium chloride) (PDDA) as a cellrepellent background. Cell culture experiments show that cortical neurons respond and bind specifically to the sPLA 2 micropatterns in competition with PLL micropatterns. The fabrication and the initial biological results on the nanofilm micropatterns support the usefulness of the technique for use in studies aimed at elucidating important biological structure-function relationships, but the applicability of the fabrication method is much broader and may impact electronics, photonics, and chemical microsystems.

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Geometric Determinants of Directional Cell Motility Revealed Using Microcontact Printing

Cited by 233 publications

References 21 publications

The effects of proteoglycan surface patterning on neuronal pathfinding

The effects of proteoglycan surface patterning on neuronal pathfinding

Chondrocyte spheroids on microfabricated PEG hydrogel surface and their noninvasive functional monitoring

Fabrication of Interdigitated Micropatterns of Self-Assembled Polymer Nanofilms Containing Cell-Adhesive Materials

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