Tuning Epithelial Cell–Cell Adhesion and Collective Dynamics with Functional DNA-E-Cadherin Hybrid Linkers

Schoenit, Andreas; Giudice, Cristina Lo; Hahnen, N.; Ollech, Dirk; Jahnke, Kevin; Göpfrich, Kerstin; Cavalcanti‐Adam, Elisabetta Ada

doi:10.1021/acs.nanolett.1c03780

Cited by 18 publications

(11 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Harnessing excellent modularity, AMR can endow cells with responsiveness to user-de ned force inputs by facilely plugging in diverse cognate ligands, e.g., peptide, protein and DNA aptamer. Different from integrin for ECM adhesion, E-cadherin is a representative adhesion molecule coordinating extracellular cell-cell junctions with actin-cytoskeleton to transmit intercellular tensile forces 34,35 . For E-cadherin-mediated force coupling, we swapped the force-reception motif of AMR with recombinant E-cadherin protein via a noncovalent IgG/Protein G bridge, namely, E-cad-AMR-c-Met (Fig.…”

Section: The Versatility Of Amr To Customize Force Input-output Programmentioning

confidence: 99%

DNA-functionalized Artificial Chimeric Mechanoreceptor for de novo Force-responsive Cellular Signalling

Yang

Wang

Tian

et al. 2023

Preprint

View full text Add to dashboard Cite

Synthetic signalling receptors enable programmable cellular responses coupling with a customized input. However, engineering a designer force-sensing receptor to rewire mechanotransduction remains largely unexplored. Herein, we introduce nongenetically engineered artificial mechanoreceptors (AMRs) capable of reprogramming non-mechanoresponsive receptor tyrosine kinases (RTKs) to sense user-defined force cues, enabling a de novo designed mechanotransduction. AMR is a modular DNA-protein chimera comprising a mechanosensing-and-transmitting DNA nanodevice grafted on natural RTKs via aptameric anchors. AMR senses intercellular tensile force via an allosteric DNA mechano-switch with tuneable piconewton-sensitive force tolerance, actuating a force-triggered dynamic DNA assembly to manipulate RTK dimerization and activate intracellular signalling. By swapping the force-reception ligands, we demonstrate the AMR-mediated activation of c-Met, a representative RTK, in response to the cellular tensile forces mediated by cell-adhesion proteins (integrin, E-cadherin) or membrane protein endocytosis (CI-M6PR). Moreover, the versatility of AMR allows the reprogramming of FGFR1, another RTK, to customize mechanobiological function, e.g., adhesion-mediated neural stem cell maintenance.

show abstract

Section: The Versatility Of Amr To Customize Force Input-output Programmentioning

confidence: 99%

DNA-functionalized Artificial Chimeric Mechanoreceptor for de novo Force-responsive Cellular Signalling

Yang

Wang

Tian

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Examples of CAMs include integrins, which assemble focal adhesions, and cadherins, which assemble adherens junctions between epithelial cells 11 – 14 . The structural complexity and functional diversity of CAMs make it unclear whether the extracellular binding and intracellular-domain-mediated cytoskeletal reorganization functions can be uncoupled and recombined to generate new cell–cell connectivities, although previous studies indicate the potential for modularity 15 – 19 .…”

Section: Mainmentioning

confidence: 99%

Programming multicellular assembly with synthetic cell adhesion molecules

Stevens

Harris

Gerdts

et al. 2022

Nature

View full text Add to dashboard Cite

Cell adhesion molecules are ubiquitous in multicellular organisms, specifying precise cell–cell interactions in processes as diverse as tissue development, immune cell trafficking and the wiring of the nervous system1–4. Here we show that a wide array of synthetic cell adhesion molecules can be generated by combining orthogonal extracellular interactions with intracellular domains from native adhesion molecules, such as cadherins and integrins. The resulting molecules yield customized cell–cell interactions with adhesion properties that are similar to native interactions. The identity of the intracellular domain of the synthetic cell adhesion molecules specifies interface morphology and mechanics, whereas diverse homotypic or heterotypic extracellular interaction domains independently specify the connectivity between cells. This toolkit of orthogonal adhesion molecules enables the rationally programmed assembly of multicellular architectures, as well as systematic remodelling of native tissues. The modularity of synthetic cell adhesion molecules provides fundamental insights into how distinct classes of cell–cell interfaces may have evolved. Overall, these tools offer powerful abilities for cell and tissue engineering and for systematically studying multicellular organization.

show abstract

“…More recently, optochemical tools were also developed to control the link between the cadherins and the actin cytoskeleton through light exposure, thus controlling cell-cell adhesion maturation [90]. Finally, the DNA technologies presented in the previous section were combined with cadherin molecules in order to modulate the association energy between cadherins without affecting their intracellular interactions: to do so, the tip of classical E-cadherins were modified to integrate DNA binders [91] of tunable length, i.e. tunable adhesion energy.…”

Section: Plasticity Control and Materials Properties Of In Vitro Mode...mentioning

confidence: 99%

Adhesion regulation and the control of cellular rearrangements: From emulsions to developing tissues

2022

View full text Add to dashboard Cite

Cell rearrangements are critical for tissue remodeling during diverse biological processes, such as morphogenesis or cancer progression. They control tissue fluidity and can lead to irreversible shape changes in cohesive tissues. However, the completion of such rearrangements is strongly conditioned by intercellular adhesion, that can prevent their completion or conversely promote them along a given pattern. In this review we explore how intercellular adhesion impacts cell rearrangements at the local scale and how it translates into macroscopic mechanical properties in biological tissues. We first describe general principles obtained from the study of dispersed materials, such as emulsions, in which the mechanical properties and interaction potential between individual particles can be described in a quantitative manner. We then review the effect of varying cell-cell adhesion on rearrangements in vitro model tissues, from cell aggregates to 2D epithelial-like cellular layers. We finally consider developing tissues in which adhesion between the cells is strongly tuned and localized in order to allow for function and shape emergence in the embryo.

show abstract

Tuning Epithelial Cell–Cell Adhesion and Collective Dynamics with Functional DNA-E-Cadherin Hybrid Linkers

Cited by 18 publications

References 59 publications

DNA-functionalized Artificial Chimeric Mechanoreceptor for de novo Force-responsive Cellular Signalling

DNA-functionalized Artificial Chimeric Mechanoreceptor for de novo Force-responsive Cellular Signalling

Programming multicellular assembly with synthetic cell adhesion molecules

Adhesion regulation and the control of cellular rearrangements: From emulsions to developing tissues

Contact Info

Product

Resources

About