Gap geometry dictates epithelial closure efficiency

Ravasio, Andrea; Cheddadi, Ibrahim; Chen, Tianchi; Pereira, Telmo; Ong, Hui Ting; Bertocchi, Cristina; Brugués, Agustí; Jacinto, António; Kabla, Alexandre; Toyama, Yusuke; Trepat, Xavier; Gov, Nir S.; Almeida, Luís; Ladoux, Benoît

doi:10.1038/ncomms8683

Cited by 129 publications

(197 citation statements)

References 63 publications

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“…“wound-healing assays”) have also revealed emergent, geometry-dependent behaviors. 77, 78, 80–82, 86–88 For instance, cells at the migration front may be “pulled” by supramolecular actomyosin cables (e.g. purse-string mechanism), 88 which act to straighten out curved migration fronts.…”

Section: Discussionmentioning

confidence: 99%

Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics

et al. 2017

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3D printed biomaterials with spatial and temporal functionality could enable interfacial manipulation of fluid flows and motile cells. However, such dynamic biomaterials are challenging to implement since they must be responsive to multiple, biocompatible stimuli. Here, we show stereolithographic printing of hydrogels using noncovalent (ionic) crosslinking, which enables reversible patterning with controlled degradation. We demonstrate this approach using sodium alginate, photoacid generators and various combinations of divalent cation salts, which can be used to tune the hydrogel degradation kinetics, pattern fidelity, and mechanical properties. This approach is first utilized to template perfusable microfluidic channels within a second encapsulating hydrogel for T-junction and gradient devices. The presence and degradation of printed alginate microstructures were further verified to have minimal toxicity on epithelial cells. Degradable alginate barriers were used to direct collective cell migration from different initial geometries, revealing differences in front speed and leader cell formation. Overall, this demonstration of 3D printing using non-covalent crosslinking may enable adaptive and stimuli-responsive biomaterials, which could be utilized for bio-inspired sensing, actuation, drug delivery, and tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics

et al. 2017

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“…Epithelial cells have been shown to extend lamellipodia for several micrometers past areas with ECM during wound healing and cell migration 31,32 . Our observations of lamellipodia extending up to 5 µm beyond adhesive regions and the pronounced actin bundles at the pattern edges match well with the spatiotemporal organization of the cytoskeleton and focal adhesions at the leading edge of migrating cells 33 .…”

Section: Discussionmentioning

confidence: 99%

Controlling cell shape on hydrogels using lift-off patterning

Moeller

Denisin

Sim

et al. 2017

Preprint

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Polyacrylamide gels functionalized with extracellular matrix proteins are commonly used as cell culture platforms to evaluate the combined effects of extracellular matrix composition, cell geometry and substrate rigidity on cell physiology. For this purpose, protein transfer onto the surface of polyacrylamide hydrogels must result in geometrically well-resolved micropatterns with homogeneous protein distribution. Yet the outcomes of micropatterning methods have not been pairwise evaluated against these criteria. We report a high-fidelity photoresist lift-off patterning method to pattern ECM proteins on polyacrylamide hydrogels ranging from 5 to 25 kPa. We directly compare the protein transfer efficiency and pattern geometrical accuracy of this protocol to the widely used microcontact printing method. Lift-off patterning achieves higher protein transfer efficiency, increases pattern accuracy, increases pattern yield, and reduces variability of these factors within arrays of patterns as it bypasses the drying and transfer steps of microcontact printing. We demonstrate that lift-off patterned hydrogels successfully control cell size and shape and enable long-term imaging of actin intracellular structure and lamellipodia dynamics when we culture epithelial cells on these substrates.

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“…SIR-Actin, a live-cell actin labeling dye was used to label the junctions. The cut was carried out by using an ImageJ plug-in to control both the actuators and the shutter [43]. Laser ablation was carried out at the z-plane of EAJs using 65 nW laser power focused at the back aperture of the objective lens with an exposure time of 350 ms. Time-lapse confocal images were acquired every 2 s, starting from 3 frames prior to the ablation until 40 frames post-ablation with a scan speed of 1 frame/s and a pinhole size of 74 µm.…”

Section: Junctional Tension Measurement By Laser Ablationmentioning

confidence: 99%

Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

Gorji

Toh

et al. 2019

Preprint

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Rationale:Failure of small synthetic vascular grafts is largely due to late endothelialization and has been an ongoing challenge in the treatment of cardiovascular diseases. Objective:Previous strategies developed to promote graft endothelialization include surface topographical modulation and biochemical modifications. However, these have been met with limited success. Importantly, although the integrity of Endothelial Cell (EC) monolayer is crucial for endothelialization, the crosstalk between surface topography and cell-cell connectivity is still not well understood. Here we explored a combined strategy that utilizes both topographical features and pharmacological perturbations. Methods and result:We characterized EC behaviors in response to micron-scale grating topography in conjunction with pharmacological perturbations of endothelial adherens junctions (EAJ) regulators. We studied the EA.hy 926 cell-cell junctions and monolayer integrity using the junctional markers upon the inhibitory effect of EAJ regulator on both planar and grating topographies substrates.We identified a protein tyrosine phosphatase, PTP1B, as a potent regulator of EAJ stability. Next, we studied the physiologically relevant behaviors of EC using primary human coronary arterial endothelial cells (HCAEC). Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration to promote endothelialization.Our results showed that PTP1B inhibition synergized with grating topographies to modulate EAJ rearrangement, thereby controlling global EC monolayer sheet orientation, connectivity and collective cell migration and proliferation. Conclusion:The synergistic effect of PTP1B inhibition and grating topographies could be useful for the promotion of endothelialization by enhancing EC migration and proliferation. IntroductionHealthy blood vessels are covered by a contiguous monolayer of endothelial cells (ECs), which maintain vasculature hemostasis and serve as a blood-compatible interface. Injured arteries and the associated EC malfunctions result in inflammatory responses, subsequent vessel thickening due to the migration and proliferation of smooth muscle cells, plaque formation, and partial or complete occlusion of the vessels [1]. Such atherosclerotic processes underlie peripheral and cardiovascular diseases, stroke, and myocardial infarction which are among the most prevalent causes of death worldwide [2,3]. Among the available treatment options, the replacement of the occluded vessel with either an autologous vein or a synthetic vascular graft has been widely practiced. However, while the implantation of large vessels has been a standard procedure, synthetic small vascular graft (diameter <6 mm) has remained problematic. The primary cause of small graft failure has been attributed to the lack of proper endothelialization [4] [5] [6]. Thus, there remains an unmet clinical need for a small vascular gra...

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Gap geometry dictates epithelial closure efficiency

Cited by 129 publications

References 63 publications

Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics

Stereolithographic printing of ionically-crosslinked alginate hydrogels for degradable biomaterials and microfluidics

Controlling cell shape on hydrogels using lift-off patterning

Enhancement of endothelialization by topographical features is mediated by PTP1B-dependent endothelial adherens junctions remodeling

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