Aleksei Aksimentiev

Assistant Professor

Ph.D. Chemistry, Institute of Physical Chemistry Polish Academy of Sciences, 1999

Professor Aksimentiev received his Ph.D in chemistry cum laude from the Institute of Physical Chemistry, Warsaw, Poland, in 1999, after completing a master's degree in particle physics at the Ivan Franko Lviv State University in his native Ukraine in 1996. 

He received postdoctoral training at the Materials Science Laboratory R&D Center of Mitsui Chemicals, Tokyo, Japan, from 1999 to 2001, when he joined the Theoretical and Computational Biophysics Group at the University of Illinois as a postdoctoral research associate. He accepted the position of assistant professor of physics at Illinois in 2005

Other Activities

Electronic recognition of DNA with synthetic nanopore sensors
In collaboration with experimentalists and theorists in electrical engineering and physics at Illinois, Professor Aksimentiev is exploring the use of nanometer-diameter artificial pores in ultrathin silicon membranes to sequence single molecules of DNA under physiological conditions. In principle, the chemical sequence of a DNA molecule can be determined by analyzing the electrical signals produced by the molecule as it squeezes through the nanopore in the membrane. Using the MOSFET fabrication technology, a low-noise amplifier can be integrated with a nanopore, enabling rapid detection and amplification of the electric signals resulting from the DNA-nanopore interaction. As a part of this highly collaborative project, Professor Aksimentiev is developing a numerical model of the nanopore sensor that will relate the measured electrical signals to the conformation and sequence of the DNA strands as they pass through the nanopore. He recently carried out the first-ever atomistic simulations of DNA translocation through synthetic nanopores. Future work will focus on developing of a computational methodology that can describe both biological macromolecules (nucleic acids, lipids, and proteins) and silicon-bases synthetic membranes, accounting for the electronic structure of the latter. This method will be applied to test the design and detection capabilities of the nanopore sensor, including investigations of optimal nanopore shapes, applied electric fields modulations, and sequence detection strategies. (Click on the illustration to download a 2.2-Mb animation of DNA translocation through a synthetic nanopore.)

Nanomechanics of molecular motors
Molecular motors are miniature devices created by nature to perform various functions in living cells. They carry out cell division, produce contractions of our muscles, transport nutrients between cell's compartments, move cells in space, etc. A common function of these diverse enzymes is the transformation of chemical energy into mechanical motion and vice versa, often performed at nearly 100% efficiency. An exemplary molecular machine FoF1-ATP synthase is a complex of two molecular motors, Fo and F1, mechanically coupled by the two common stalks (see figure). The membrane embedded Fo unit efficiently converts the proton-motive force into mechanical rotation of the central stalk inside the solvent-exposed F1 unit. This rotation causes cyclic conformational changes in F1, thereby driving synthesis of ATP. As ATP it produces is used to fuel other cellular processes, this enzyme is central for cellular function. In collaboration with a group at the University of Wisconsin, Professor Aksimentiev investigated energy conversion in the molecular machine FoF1-ATP synthase by combining large-scale molecular dynamics with a mathematical model built on stochastic equations of motion to simulate the physiological function of the enzyme. This multiple time scale computational methodology will be deployed to investigate the molecular mechanism of energy transduction in sodium and V-type ATPases, which high-resolusion X-ray structures became recently available. (Click on the illustration to download a 6.2Mb animation of the Fo unit rotation.)

Transport across cell membranes
Compartmentalization is a key principle for the functional organization of living cells. Transport across compartmental boundaries and, in particular, across the cell wall is controlled by membrane proteins that act as selective channels and transporters. Puncturing the boundaries leads to pathologies, e.g., in the case of toxins, but is also an opportunity for treatment, e.g., in the case of antimicrobial peptides. The ability of membrane channels to sort single molecules is of great interest in bioengineering and, as a result, membrane channels like alpha-hemolysin have been adopted for in vitro devices or used as an inspiration for manufacturing artificial channels. Thus, suspended in a lipid bilayer, an alpha-hemolysin channel becomes a stochastic sensor when a molecular adapter is placed inside its genetically re-engineered transmembrane pore, reporting via modulation of the transmembrane ionic current the type and the concentration of analytes entering the channel. The transmembrane pore of alpha-hemolysin can conduct not only small solutes, but also rather big (tens of kDa) linear macromolecules, including DNA and RNA strands. Using alpha-hemolysin as a prototypical beta-barrel membrane channel, Professor Aksimentiev is investigating transport of ions, nucleic acids and proteins across the cells boundaries. In collaboration with leading experimental groups, he has been conducting large scale molecular dynamics simulation of nucleic acids transport. In the future, he will apply this computational methodology to investigate translocation of proteins through membrane pores. (Click on the illustration to download a 4.1-Mb animation of DNA translocation through a membrane channel.)

Additional Information

Accomplishments: demonstrated the feasibility of sequencing DNA using a nanopore capacitor (Nano Letters 8:56), and detecting single nucleotide polymorphism using restriction enzymes (Nano Letters 6:1680). Developed a method for studying the stress-strain dependence of long biomolecular filaments (Submitted), steering transmembrane transport of solutes with a grid-derived force (J. Chem. Phys. 127:125101). Elucidated the structure of the bacterial adhesin OpcA (Biophysical Journal 93:3058, Cover). The three projects (calcium pump, artificial ion channel, and DNA hairpin) that are led by the second and third year graduate students are taking speed; publications are being prepared for submission.

For more information:

http://www.ks.uiuc.edu/~alek/

Honors and awards:

• IBM Faculty Fellow Award

Selected Publications:

• B. Luan and A. Aksimentiev. Electric and electrophoretic inversion of the DNA charge in multivalent electrolytes. Soft Matter, in press (2009).
• B. Luan, R. Carr, M. Caffrey and A. Aksimentiev. The effect of calcium on the conformation of cobalamin transporter BtuB. Protein: Structure, Function, and Bioinformatics, in press (2009).
• B. Dorvel, G. Sigalov, Q. Zhao, J. Comer, V. Dimitrov, U. Mirsaidov, A. Aksimentiev and G. Timp. Analyzing the forces binding restriction endonucleases to DNA using a synthetic nanopore. Nucleic Acid Research 37, 4170-4179 (2009).
• C. Maffeo and A. Aksimentiev. Structure, dynamics, and ion conductance of a phospholamban pentamer. Biophysical Journal 96, 4853-4865(2009) .
• A. Aksimentiev, R. Brunner, E. R. Cruz-Chu, J. Comer and K. Schulten. Modeling Transport Through Synthetic Nanopores. IEEE Nanotechnology Magazine, 3, 21-28 (2009)
• E. R. Cruz-Chu, A. Aksimentiev, and K. Schulten. Ionic current rectification through silica nanopores. Journal of Physical Chemistry C, 113 1850-1862 (2009).
• J. Comer, V. Dimitrov, G. Timp, and A. Aksimentiev. Microscopic mechanics of hairpin DNA tranlocation through synthetic nanopores. Biophysical Journal 96, 593–608 (2009).
• B. Luan and A. Aksimentiev. DNA attraction in monovalent and divalent electrolytes. Journal of the American Chemical Society 130:15754-15755 (2008).
• R. Carr, I. A. Weinstock, A. Sivaprasadarao, A. Muller and A. Aksimentiev Self-assembly route for embedding polyoxomolybdate capsules in lipid bilayer membranes. Nano Letters 8:3916-3921(2008).
• B. Luan and A. Aksimentiev. Strain softening in stretched DNA. Physical Review Letters 101:118101 (2008).
• G. Sigalov, J Comer, G. Timp, and A. Aksimentiev. Detection of DNA sequences using an alternating electric field in a nanopore capacitor. Nano Letters 8:56-63 (2008).
• David Wells, Volha Abramkina, and Aleksei Aksimentiev. Exploring transmembrane transport through alpha-hemolysin with grid-steered molecular dynamics. J. Chem. Phys.127:125101-10 (2007).