(7o) Decoding the Nature-Designed Codes in Membranes: Applications in Biomedicines and Bioengineering

Authors: 
Sachan, A. K., University of Minnesota
Research Interests:

The bilayer cell membranes and the monolayer membranes existing at the air-aqueous interfaces in the biological system, such as alveolar interface in lungs, are fascinating examples of nature-designed two-dimensional heterogeneous complex fluids equipped with remarkable properties. How different lipids and proteins specifically and stoichiometrically interact with each other and form static and/or dynamic macromolecular assemblies in membranes have intrigued me over the years, and are the emerging area of membrane research. Cell membrane of each type of cell lines possesses its own unique macromolecular assemblies of lipids/proteins. Moreover, specific macromolecular assemblies in cell membranes of either cell line have their own spatial and temporal regulation based on the activity level, ageing and/or state of health of cells. Similarly, lipids/proteins monolayer (lung surfactant) lying at the air-aqueous interfaces of alveoli in each air-breathing mammals possesses their own specific ratios of constituents. The composition, and the mechanical and physical properties of these lung surfactants evolve with the age, activity and the state of health as well. Therefore, specific and stoichiometric arrangement of lipid and protein molecules in a two-dimensional monolayer and bilayer membranes imparts not only specialized architecture and function to the membranes but also localized nano- to micro-structural hot spots of physical and chemical forces to these soft materials. I believe we can harness such nano- to micro-scale hot spots of unique physical and chemical force maps present on the two-dimensional landscape of membranes for diagnostic and pharmaceutical purposes, as cells utilize membrane-based chemical and physical force maps during migration and specific cell-cell communication.

Future Direction:

My academic career training has been an amalgam of diverse fields of science and engineering, such as materials science, soft-matter physics, biochemistry, biophysics and human physiology and pathology. My strength as a researcher lies in my critical thinking and inherent problem-solving skills. As a researcher I would continue to apply those skills along with multidisciplinary approach for understanding the nature-designed structures, exploring their potentials in different areas of bioengineering and biomedicine, as well as creating biomimetic devices for industrial applications. I would unite and orchestrate the knowledge gained over the period of my academic career in soft-matter physics of membranes for: exploring the hidden potentials in nature-designed two-dimensional monolayer and bilayer membranes.

Although the optical microscopy techniques have improved resolutions, probe-based Atomic force microscopy (AFM) technique is still the highest resolution tool for observing and revealing hierarchical organization of lipids and proteins in cell membranes. Driven by its immense potential and the requirement of scientific community, the AFM technique since its invention in 1980’s has been developed for many specialized applications in materials science, such as scanning ion-conductance microscopy, Kelvin probe force microscopy (KPFM), Electrochemical force microscopy, scanning near-field optical microscopy, scanning capacitance microscopy, magnetic force microscopy, just to name some. During my PhD research, I extensively exploited AFM’s high-resolution imaging, material characterization and nano-manipulation modes to probe the nanoscale structures in monolayer and multilayered lipids/protein membrane. In addition, I customized the state-of-the-art KPFM technique to unveil the contact potential differences at submicron resolution over the nanoparticle clusters embedded in multilayered structures of lipids. My research lab will customize the probe-based state-of-the-art nanoscopy techniques to characterize the membrane surfaces as well as invest in development of innovative surface characterization techniques and methodology to probe the sub-micron surface properties of native as well as artificial complex membrane models. Revelation of the map of spatial distribution of physical forces on the membrane along with high-resolution structural organization can be breakthrough in translational research and bioengineering. Detailed information will be presented at poster session.

Teaching Interests:

The very first task of teaching I took was self-appointed when I had decided to offer free physics and chemistry classes to socio-economically weak students of high school and senior secondary (10+2) level in 2004, which helped me realize the essence of being a teacher and different challenges involved. Thereafter I gained extensive teaching and mentoring experience. At higher levels, my significant teaching experiences are: 1) appointed as a teaching assistant (TA) for Electrophysiology laboratory course to participating PhD researchers at Physiology of Nerve Cells Workshop organized by the SERC-DST in 2009 at the Indian Institute of Science, Bangalore. 2) Mentoring and teaching assistant to undergraduate and graduate students during my PhD research at the University of Muenster, Germany, where I taught lecture courses on Biophysical techniques, especially Atomic force microscopy and Dark-field electron microscopy, and a lab course on Ultramicrotomy technique. 3) Mentored the directed research of two graduate (PhD) and three undergraduate students during my current postdoctoral research.

As a faculty, I will be delighted to teach courses related to biomedical field, bioengineering, soft-matter physics of membrane and my own research projects: fundamentals of membrane, membranes and their pharmaceutical importance, interfacial rheology and mechanics, nature-inspired bioengineering, and biophysical techniques.

Successful Grant Proposals: Contributed in writing with novel ideas, theories and results in successful NIH R01 (graded 1-2 on Innovation scale by the reviewers) and NSF grant applications submitted by PI.

Postdoctoral Project: “Shear and Dilatational Rheology of 2-D Fluid Membranes at Planar and Curved Interfaces and Their Relation with Micro-structures.”

Principal Investigator: Prof. Joseph A. Zasadzinski, Chemical Engineering and Materials Science, University of Minnesota.

PhD Research: “Functional Nanostructures of Pulmonary Surfactant Monolayer Membrane and Its Interaction with Nanoparticles: Atomic Force Microscopy Investigation.”

Under supervision of Prof. Hans-Joachim Galla, Institute of biochemistry, and Prof. Rudolf Reichelt, Institute of medical physics and biophysics, University of Muenster, Germany.

Peer-reviewed Publications:

Sachan A. K. and Zasadzinski J. A. (2017). Interfacial Curvature Effects on Morphology and Dynamics of Monolayer Membrane. (Under review in PNAS)

Sachan A. K., Choi S. Q., Kim K. H., Tang Q., Hwang L., Lee K. Y. C., Squires T. M., Zasadzinski J. A. (2017). Interfacial Rheology of Coexisting Solid and Fluid Monolayers. Soft Matter 13 (7), 1481-1492.

Sachan A. K.* and Galla H. J. (2014). Understanding the Mutual Impact of Interaction between Hydrophobic Nanoparticles and Pulmonary Surfactant Monolayer. Small 10 (6), 1069-75.

Cramer S., Tacke S., Bornhorst J., Sachan A. K., Klingauf J., Schwerdtle T., Galla H. J. (2014). The Influence of Silver Nanoparticles on the Blood-Brain and the Blood-Cerebrospinal Fluid Barrier in vitro. Journal of Nanomedicine & Nanotechnology 5 (5), 1- 12.

Sachan A. K. and Galla H. J. (2013). Bidirectional Surface Analysis of Monomolecular Membrane Harboring Nanoscale Reversible Collapse Structures. Nano Letters 13 (3), 961–966.

Sachan A. K., Harishchandra R. K., Bantz C., Maskos M., Reichelt R., Galla H. J. (2012). High-Resolution Investigation of Nanoparticle Interaction with a Model Pulmonary Surfactant System. ACS Nano 6 (2), 1677–1687.

Harishchandra R. K., Sachan A. K., Kerth A., Lentzen G., Neuhaus T., Galla H. J. (2011). Compatible Solutes: Ectoine and Hydroxyectoine Improve Functional Nanostructures in Artificial Lung Surfactants. BBA – Biomembranes 1808 (12), 2830–2840.