Image recovery from unknown network mechanisms for DNA sequencing-based microscopy.

Imaging-by-sequencing methods are an emerging alternative to conventional optical micro- or nanoscale imaging. In these methods, molecular networks form through proximity-dependent association between DNA molecules carrying random sequence identifiers. DNA strands record pairwise associations such that network structure may be recovered by sequencing which, in turn, reveals the underlying spatial relationships between molecules comprising the network.

Stochastic modeling of antibody binding predicts programmable migration on antigen patterns.

Viruses and bacteria commonly exhibit spatial repetition of surface molecules that directly interface with the host immune system. However the complex interaction of patterned surfaces with immune molecules containing multiple binding domains is poorly understood. We developed a pipeline for constructing mechanistic models of antibody interactions with patterned antigen substrates.

Tuning intercellular adhesion with membrane-anchored oligonucleotides.

Adhesive interactions between cells play an integral role in development, differentiation and regeneration. Existing methods for controlling cell-cell cohesion and adhesion by manipulating protein expression are constrained by biological interdependencies, e.g.

A computational framework for DNA sequencing microscopy.

We describe a method whereby microscale spatial information such as the relative positions of biomolecules on a surface can be transferred to a sequence-based format and reconstructed into images without conventional optics. Barcoded DNA "polymerase colony" (polony) amplification techniques enable one to distinguish specific locations of a surface by their sequence. Image formation is based on pairwise fusion of uniquely tagged and spatially adjacent polonies.

Publisher Correction: Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies.

In the Supplementary Information file originally published with this Article, the Supplementary references 48-62 were missing; the amended file has now been uploaded.

Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies.

Although repetitive patterns of antigens are crucial for certain immune responses, an understanding of how antibodies bind and dynamically interact with various spatial arrangements of molecules is lacking. Hence, we introduced a new method in which molecularly precise nanoscale patterns of antigens are displayed using DNA origami and immobilized in a surface plasmon resonance set-up. Using antibodies with identical antigen-binding domains, we found that all the subclasses and isotypes studied bind bivalently to two antigens separated at distances that range from 3 to 17 nm.

Solution-Controlled Conformational Switching of an Anchored Wireframe DNA Nanostructure.

Self-assembled DNA origami nanostructures have a high degree of programmable spatial control that enables nanoscale molecular manipulations. A surface-tethered, flexible DNA nanomesh is reported herein which spontaneously undergoes sharp, dynamic conformational transitions under physiological conditions. The transitions occur between two major macrostates: a spread state dominated by the interaction between the DNA nanomesh and the BSA/streptavidin surface and a surface-avoiding contracted state.

Technological complexity and the global dispersal of modern humans.

Anatomically modern humans (Homo sapiens) dispersed out of Africa roughly 120,000 years ago and again after 75,000 years ago. The early dispersal was geographically restricted to the Arabian Peninsula, Levant, and possibly parts of southern Asia. The later dispersal was ultimately global in scope, including areas not previously occupied by Homo.

Sequence-specific nuclease-mediated release of cells tethered by oligonucleotide phospholipids.

Single-stranded oligonucleotide-conjugated lipids (ssDNA-PEG-lipids) that associate with the cell membrane confer to the cell an artificial adhesive capability via sequence-specific hybridization to complementary oligonucleotides, forming bonds of double stranded oligonucleotides (dsDNA). Such artificial tethers permit surface patterning of cells or controlled formation of cellular aggregates. However, the hybridization responsible for tethering cells to surfaces or to other cells is not trivially reversed under physiological conditions.

Manipulation of cell sorting within mesenchymal stromal cell-islet cell multicellular spheroids.

Colocalization of islets with immunoprivileged cell types such as mesenchymal stromal cells (MSCs) is a potentially multifaceted and adaptive approach to islet protection. We attempted to colocalize MSCs with islets by creating single-celled suspensions of MSCs and cells from dissociated islets on top of arrays of round-bottomed wells. Segregation between islet-derived cells and MSCs was observed within 3 days.

Long term culture of cells patterned on glass via membrane-tethered oligonucleotides.

Oligonucleotide-based membrane inserts can be used as tethers to control attachment of cells to patterned surfaces without interfering with internal cytoskeletal modes of adhesion. Such control can be employed as a means for study of cell-cell interactions or side-by-side co-culture of different cell types without separation/sorting. While there is utility for cell patterning methods decoupled from natural cytoskeletal mechanisms, the consequences of maintaining this artificially induced state of attachment remains unexplored.

Assessing the spatial resolution of cellular rigidity sensing using a micropatterned hydrogel-photoresist composite.

The biophysical machinery that permits a cell to sense substrate rigidity is poorly understood. Rigidity sensing of adherent cells likely involves traction forces applied through focal adhesions and measurement of resulting deformation. However, it is unclear if this measurement takes place underneath single focal adhesions, over local clusters of focal adhesions, or across the length of the entire cell.

Presence of pores and hydrogel composition influence tensile properties of scaffolds fabricated from well-defined sphere templates.

Sphere templating is an attractive method to produce porous polymeric scaffolds with well-defined and uniform pore structures for applications in tissue engineering. While high porosity is desired to facilitate cell seeding and enhance nutrient transport, the incorporation of pores will impact gross mechanical properties of tissue scaffolds and will likely be dependent on pore size. The goals of this study were to evaluate the effect of pores, pore diameter, and polymer composition on gross mechanical properties of hydrogels prepared from crosslinked poly(ethylene glycol) (PEG) and poly(2-hydroxyethyl methacrylate) (pHEMA).