Igal Szleifer - Academia.edu (original) (raw)

Papers by Igal Szleifer

Biophysical Journal, 2020

Polymers, 2022

Protein adsorption onto nanomaterials is a process of vital significance and it is commonly contr... more Protein adsorption onto nanomaterials is a process of vital significance and it is commonly controlled by functionalizing their surface with polymers. The efficiency of this strategy depends on the design parameters of the nanoconstruct. Although significant amount of work has been carried out on planar surfaces modified with different types of polymers, studies investigating the role of surface curvature are not as abundant. Here, we present a comprehensive and systematic study of the protein adsorption process, analyzing the effect of curvature and morphology, the grafting of polymer mixtures, the type of monomer (neutral, acidic, basic), the proteins in solution, and the conditions of the solution. The theoretical approach we employed is based on a molecular theory that allows to explicitly consider the acid–base reactions of the amino acids in the proteins and the monomers on the surface. The calculations showed that surface curvature modulates the molecular organization in spac...

Journal of biomedical materials research. Part A, Jan 2, 2018

There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to h... more There is a need in orthopaedic and craniomaxillofacial surgeries for materials that are easy to handle and apply to a surgical site, can fill and fully conform to the bone defect, and can promote the formation of new bone tissue. Thermoresponsive polymers that undergo liquid to gel transition at physiological temperature can potentially be used to meet these handling and shape-conforming requirements. However, there are no reports on their capacity to induce in vivo bone formation. The objective of this research was to investigate whether the functionalization of the thermoresponsive, antioxidant macromolecule poly(poly-ethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN), with strontium, phosphate, and/or the cyclic RGD peptide would render it a hydrogel with osteoinductive properties. We show that all formulations of functionalized PPCN retain thermoresponsive properties and can induce osteodifferentiation of human mesenchymal stem cells without the need for exogenous osteogeni...

Nature biomedical engineering, 2017

Many human diseases result from the dysregulation of the complex interactions between tens to tho... more Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complet...

PloS one, 2017

Ligand-receptor binding is of utmost importance in several biologically related disciplines. Liga... more Ligand-receptor binding is of utmost importance in several biologically related disciplines. Ligand binding assays (LBA) use the high specificity and high affinity of ligands to detect, target or measure a specific receptors. One particular example of ligand binding assays are Antibody conjugated Nanoparticles (AcNPs), edge-cutting technologies that are present in several novel biomedical approaches for imaging, detection and treatment of diseases. However, the nano-confinement in AcNPs and LBA nanostructures introduces extra complexity in the analysis of ligand-receptor equilibriums. Because antibodies are large voluminous ligands, the effective affinity in AcNPs is often determined by antibody orientation and surface coverage. Moreover, antibodies have two binding sites introducing an extra ligand-receptor binding equilibrium. As consequence of all this, experimental or theoretical studies providing a guidelines for the prediction of the binding behavior in AcNPs are scarce. In th...

Biomaterials Science, 2013

One of the key challenges in the development of nano carriers for drug delivery and imaging is th... more One of the key challenges in the development of nano carriers for drug delivery and imaging is the design of a system that selectively binds to target cells. A common strategy is to coat the delivery device with specific ligands that bind strongly to overexpressed receptors. However such devices are usually unable to discriminate between receptors found on benign and malignant cells. We demonstrate, theoretically, how one can achieve enhanced binding to target cells by using multiple physical and chemical interactions. We study the effective interactions between a polymer decorated nano micelle or nanoparticle with three types of model lipid membranes that differ in the composition of their outer leaflet. They are: i) lipid membranes with overexpressed receptors, ii) membranes with a given fraction of negatively charged lipids and iii) membranes with both overexpressed receptors and negatively charged lipids. The coating contains a mixtures of two short polymers, one neutral for protection and the other a polybase with a functional end-group to optimize specific binding with the overexpressed receptors and electrostatic interactions with charged lipid head-groups. The strength of the binding for the combined system is much larger than the sum of the independent electrostatic or specific interactions binding. We find a range of distances where the addition of two effective repulsive interactions become an attraction in the combined case. The changes in the strength and shape of the effective interaction are due to the coupling that exists between molecular organization, physical interactions and chemical state, e.g., protonation. The predictions provide guidelines for the design of carrier devices for targeted drug and nanoparticle delivery and give insight in the competing and highly non-additive nature of the different effective interactions in nanoscale systems in constrained environments that are ubiquitous in synthetic and biological systems.

Proceedings of the National Academy of Sciences, 1998

Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and p... more Spontaneous liposome formation is predicted in binary mixtures of fluid phase phospholipids and poly(n)ethylene oxide (PEO)-bearing lipids by using single chain mean field theory. The range of stability of the spontaneous liposomes is determined as a function of percentage of PEO-conjugated lipids and polymer molecular weight. These predictions were tested by using cast films of 1,2-diacyl- sn -glycerophosphocholines (e.g., egg l -α-lecithin, 1,2-dimyristoyl- sn -glycero-3-phosphocholine, 1,2-dipalmitoyl- sn -glycero-3-phosphocholine, and 1,2-distearoyl- sn -glycero-3-phosphocholine) and 1,2-dipalmitoyl- sn -glycerophosphatidylethanolamine-PEO conjugates (i.e., 1,2-dipalmitoyl- sn -glycero-3-phosphoethanolamine- N -[methoxypoly(ethylene glycol)2000]carboxamide and 1,2-dipalmitoyl- sn -glycero-3-phosphoethanolamine- N -[methoxypoly(ethylene oxide)5000]carboxamide) that were hydrated above their gel-liquid crystal phase transition temperatures. Particle sizes of the resulting dispersi...

Experimental cell research, Sep 30, 2017

Chemical fixation is nearly indispensable in the biological sciences, especially in circumstances... more Chemical fixation is nearly indispensable in the biological sciences, especially in circumstances where cryo-fixation is not applicable. While universally employed for the preservation of cell organization, chemical fixatives often introduce artifacts that can confound identification of true structures. Since biological research is increasingly probing ever-finer details of the cellular architecture, it is critical to understand the nanoscale transformation of the cellular organization due to fixation both systematically and quantitatively. In this work, we employed Partial Wave Spectroscopic (PWS) Microscopy, a nanoscale sensitive and label-free live cell spectroscopic-imaging technique, to analyze the effects of the fixation process through three commonly used fixation protocols for cells in vitro. In each method investigated, we detected dramatic difference in both nuclear and cytoplasmic nanoarchitecture between live and fixed states. But significantly, despite the alterations i...

Biomedical optics express, 2016

The microscopic structural origins of optical properties in biological media are still not fully ... more The microscopic structural origins of optical properties in biological media are still not fully understood. Better understanding these origins can serve to improve the utility of existing techniques and facilitate the discovery of other novel techniques. We propose a novel analysis technique using electron microscopy (EM) to calculate optical properties of specific biological structures. This method is demonstrated with images of human epithelial colon cell nuclei. The spectrum of anisotropy factor g, the phase function and the shape factor D of the nuclei are calculated. The results show strong agreement with an independent study. This method provides a new way to extract the true phase function of biological samples and provides an independent validation for optical property measurement techniques.

Cancer research, Oct 1, 2016

Results have historically shown a broad plasticity in the origin of tumors and their functions, w... more Results have historically shown a broad plasticity in the origin of tumors and their functions, with significant heterogeneity observed in both morphologies and functional capabilities. Largely unknown, however, are the mechanisms by which these variations occur and how these events influence tumor formation and behavior. Contemporary views on the origin of tumors focus mainly on the role of particular sets of driver transformations, mutational or epigenetic, with the occurrence of the observed heterogeneity as an accidental byproduct of oncogenesis. As such, we present a hypothesis that tumors form due to heterogeneous adaptive selection in response to environmental stress through intrinsic genomic sampling mechanisms. Specifically, we propose that eukaryotic cells intrinsically explore their available genomic information, the greater genomic landscape (GGL), in response to stress under normal conditions, long before the formation of a cancerous lesion. Finally, considering the inf...

Proceedings of the National Academy of Sciences of the United States of America, Oct 4, 2016

The organization of chromatin is a regulator of molecular processes including transcription, repl... more The organization of chromatin is a regulator of molecular processes including transcription, replication, and DNA repair. The structures within chromatin that regulate these processes span from the nucleosomal (10-nm) to the chromosomal (>200-nm) levels, with little known about the dynamics of chromatin structure between these scales due to a lack of quantitative imaging technique in live cells. Previous work using partial-wave spectroscopic (PWS) microscopy, a quantitative imaging technique with sensitivity to macromolecular organization between 20 and 200 nm, has shown that transformation of chromatin at these length scales is a fundamental event during carcinogenesis. As the dynamics of chromatin likely play a critical regulatory role in cellular function, it is critical to develop live-cell imaging techniques that can probe the real-time temporal behavior of the chromatin nanoarchitecture. Therefore, we developed a live-cell PWS technique that allows high-throughput, label-fr...

Soft Matter, 2016

In this work, we study the swelling of hydrogel nanofilms in the presence of an external electric... more In this work, we study the swelling of hydrogel nanofilms in the presence of an external electric field. For this purpose, we use a theory that accounts for size, shape, conformation and charge distribution of all molecular components, in particular the polymer backbone. This molecular theory is described in our recent work, where we

Aps Meeting Abstracts, Mar 1, 2007

the surface of inorganic nanoparticles with polymer brushes improves the dispersion of the partic... more the surface of inorganic nanoparticles with polymer brushes improves the dispersion of the particles in a polymer matrix. Since improved dispersion is critical to the enhancement in material properties of the resultant nanocomposite, we are motivated to study the thermodynamics of the interface structure in the polymer particle system since the interface itself is a major determinant of nanocomposite properties. We will present the results from recent and ongoing SCMF studies on a model polymer nanocomposite system with grafted particles and explore the thermodynamics of the particle/chain miscibility region along with explicit knowledge of the polymer chain structures (both matrix and grafted). Dependence on various parameters such as the molecular weights of the grafted and matrix chains respectively, the density of the grafted chains and the particle size will also be explored.

Aps March Meeting Abstracts, Mar 1, 1998

Bulletin of the American Physical Society, Mar 6, 2015

The Journal of Chemical Physics, 2011

Journal of biophotonics, Jan 25, 2016

A new multimodal confocal microscope has been developed, which includes a parallel Partial Wave S... more A new multimodal confocal microscope has been developed, which includes a parallel Partial Wave Spectroscopic (PWS) microscopy path. This combination of modalities allows molecular-specific sensing of nanoscale intracellular structure using fluorescent labels. Combining molecular specificity and sensitivity to nanoscale structure allows localization of nanostructural intracellular changes, which is critical for understanding the mechanisms of diseases such as cancer. To demonstrate the capabilities of this multimodal instrument, we imaged HeLa cells treated with valinomycin, a potassium ionophore that uncouples oxidative phosphorylation. Colocalization of fluorescence images of the nuclei (Hoechst 33342) and mitochondria (anti-mitochondria conjugated to Alexa Fluor 488) with PWS measurements allowed us to detect a significant decrease in nuclear nanoscale heterogeneity (Σ), while no significant change in Σ was observed at mitochondrial sites. In addition, application of the new mult...

Investigacion Joven, Feb 8, 2015

Los nanocanales de estado sólido consisten en orificios que atraviesan una membrana de lado a lad... more Los nanocanales de estado sólido consisten en orificios que atraviesan una membrana de lado a lado. Típicamente la longitud del nanocanal, 10