MULTIVALENT ANTIBODY/ANTIGEN BINDING KINETICS WITH DNA ORIGAMI
Using DNA origami, it was possible to pattern and modulate spacing of antigens in a controlled reproducible manner. We could then examine the multivalent binding kinetics of antibodies with surface plasmon resonance like never before. My role in the paper was to model the kinetics, calibrate it with real data (left), and generate estimates of the underlying distribution of microstates comprising each point in time.
A. Shaw, I.T. Hoffecker, I. Smyrlaki, J. Rosa, A. Grevys, D. Bratlie, I. Sandlie, T. E. Michaelsen, J. T. Andersen, B. Högberg* Binding to nanopatterned antigens is dominated by the spatial tolerance of antibodies Nature Nanotechnology. , 1 , 2019
OPTICS-FREE MICROSCOPY USING DNA SEQUENCING
The idea behind this project is to invent a new kind of microscopy that uses DNA sequences instead of light as the primary medium of information transmission. The paper is a computational proof of concept that a dense saturated surface of polonies could be used to store spatial information on a surface that could then be reconstructed into whole images after sequencing and computational processing.
I.T. Hoffecker, Y. Yang, G. Bernardinelli, P. Orponen, B. Högberg* A Computational Framework for DNA Sequencing-Based Microscopy BioRxiv. , , 2018
USING SOLUTIONS TO TOGGLE OPENING AND CLOSING OF A DNA NANOSTRUCTURE
By manipulating solution conditions, we could open and close a tethered DNA nanostructure. We used DNA PAINT and image classification to characterize the transitions.
I.T. Hoffecker, S. Chen, A. Gådin, A. Bosco, A. I. Teixeira*, B. Högberg* Solution‐Controlled Conformational Switching of an Anchored Wireframe DNA Nanostructure Small. 03628 , , 2018
ENTROPY, COMPLEXITY, AND FUNCTION IN EARLY HUMAN TECHNOLOGY
Structural organization has always been used to extract inferences about the function of biological phenomena. We take a formal approach to this idea with different metrics of complexity to characterize early the technology of early humans and discuss how this sheds light on the problems they faced.
J. F. Hoffecker, I.T. Hoffecker The Structural and Functional Complexity of Hunter-Gatherer Technology Journal of Archaeological Method and Theory. 25 , 202-225 , 2018
APPLYING INFORMATION THEORY TO HUMAN EVOLUTION
Information, automata, and computation theory have shed light on nearly every corner of biological science...except archaeology. That is, until now! In this paper we examine the global dispersal of modern humans through the lens of computational complexity as it applies to early human technologies.
J. F. Hoffecker, I.T. Hoffecker Technological complexity and the global dispersal of modern humans Evolutionary Anthropology: Issues, News, and Reviews. 26 , 285-299 , 2017
PROGRAMMABLE CELL ATTACHMENT AND SEVERING
In this paper, we explore methods to cleave DNA mediating artificial attachment of DNA-lipid-modified cells to flat substrates or other cells. We used BamHI to sever the DNA tethers of cells bearing the correct BamHI recognition site while leaving other tethered cells alone. We also used Benzonase, a powerful nonspecific nuclease, to digest all the tethers and detach cells irrespective of their anchor sequences. Now we have a way to programmably attach and detach cells!
I.T. Hoffecker, N. Takemoto, Y. Arima, H. Iwata* Sequence-specific nuclease-mediated release of cells tethered by oligonucleotide phospholipids Biomaterials. 53 , 318-329 , 2015
PATTERNING SOFT GELS WITH STIFF ISLANDS To examine the rigidity sensing mechanisms of cells, I previously designed a method for producing micropatterned arrays of rigid photoresist islands grafted to an underlying hydrogel of tunable stiffness. The islands can be made adhesive to cells while the exposed hydrogel is left inert. This is the detailed protocol for producing such substrates.
S. Wong, W.H. Guo, I.T. Hoffecker, Y.L. Wang* Preparation of a micropatterned rigid-soft composite substrate for probing cellular rigidity sensing Methods Cell Biol. 121 , 3-15 , 2014
INDUCING MAJOR CHANGES IN CELL SORTING PATTERNS Cell sorting is a process where cells of different types spontaneously undergo relative migration, leading to distinct multicellular domains of differing cell type composition. The range of cell-cell communication is limited, and global patterns emerge due to the iteration of interactions between neighbors. We observed major changes in global sorting patterns after pharmacologically inducing changes in the individual cell-cell cohesive interactions.
I.T. Hoffecker, H. Iwata* Manipulation of cell sorting in mesenchymal stromal cell-islet cell co-aggregate spheroids Tissue Engineering Part A. 20 , 1643-1653 , 2014
DNA-LIPID-MEDIATED ADHESION vs INTEGRIN-MEDIATED ADHESION We induced an artificial form of adhesion between cells modified with ssDNA-lipids and substrates inkjet-printed with complementary ssDNA. When incubated without serum or adhesive proteins in the media, cells took on a bizarre dendrite-like morphology. When in the presence of serum proteins, cells slowly pulled away from their DNA anchors leaving trails of lipid matter behind. This study demonstrates the clear and interesting distinction between natural and artificially induced forms of adhesion.
K. Sakurai, I.T. Hoffecker, H. Iwata* Long term culture of cells patterned on glass via membrane-tethered oligonucleotides Biomaterials. 34 , 361-370 , 2013
CELL RIGIDITY SENSING IS BLIND TO FINE DETAILS Do cell focal adhesion contain molecular mechanical sensors to measure the intrinsic stiffness of their underlying substrates? Perhaps not. We built micropatterned arrays of rigid islands of sub-cellular size grafted to a soft underlying hydrogel. Though their adhesive contact was restricted to the islands, the cells on these patterns behaved as they would on uniformly soft substrates, apparently ignoring the intrinsic stiffness of the islands. You could say that cells 'pull' their substrates rather than 'pinching' them.
I.T. Hoffecker, W.H. Guo, Y.L. Wang* Assessing the spatial resolution of cellular rigidity sensing using a micropatterned hydrogel-photoresist composite Lab Chip. 11 , 3538-3544 , 2011
MECHANICS OF POROUS HYDROGEL SCAFFOLDS Preparing hydrogel scaffolds with pores via sphere-templating reduced the elastic modulus and ultimate tensile stress but interestingly increased ultimate tensile strain. We looked at several parameters such as polymer type, pore diameter, and gel crosslinking density and examined their effect on scaffold mechanical properties. Our results will help guide better hydrogel scaffold designs for tissue engineering.
S.M. LaNasa, I.T. Hoffecker, S.J. Bryant* The role of pore size on the mechanical properties of porous poly(ethylene glycol) and poly(2-hydroxyethyl methacrylate) hydrogels Journal of Biomedical Materials Research - Part B: Applied Biomaterials. 96B , 294-302 , 2011