Molecular Recognition in Biological Systems and Bioinformatics

Structure of stFRET, a cassette to measure stress in proteins in real time.

Protein structure and function; voltage-sensitive ion channels; mechano-sensitive ion channels; ligand gated ion channels; natural products pharmaceuticals; AFM; kinetic modeling software; anatomy; FRET; digital image processing; cell mechanics; advanced instrumentation for cell biophysics; electron microscopy; molecular biology of structural proteins; patch clamp.

My interests center on mechanical and electrical biophysics, from molecules to organs, and the development of new tools. And, in recent years I worked in transitional science, bringing basic science to the clinic and to industry. My basic research interests are on cell mechanics and the mechanisms by which mechanical forces are transduced into messages such as voltage and chemicals such as ATP and Ca²⁺. I discovered mechanosensitive ion channels in 1983. My methodology has included patch clamp, high resolution bright field light microscopy, low light fluorescence microscopy, high speed digital imaging, TIRF, digital image analysis, high voltage EM with tomography, Atomic Force Microscopy, molecular biology, natural product and recombinant protein biochemistry, NMR and microfabrication and microfluidics. We discovered the only known specific inhibitor of mechanosensitive ion channels and uncovered its remarkable mode action by using a combination of electrophysiology and chiral chemistry. We have demonstrated potential clinical applications of the peptide for cardiac arrhythmias, oncology, muscular dystrophy, and incontinence.

AFMs, low light cameras, micromanipulators, HPLC, FPLC, Patch clamps, lab robot, spectrofluorimeter, cell volume sensor, Coulter counter, temperature jump chips

64 node PC cluster, 15 PCs with printers, large format 2D printer, 3D printer, kinetic analysis software www.qub.buffalo.edu

Cell lines, C. Elegans, mouse

• TREK, collagen, flipin, actinin, spectrin, ICK peptides
• For those of you who don't know that they are not proteins, we also study lipids and membranes.

Arrhythmias, blood pressure, touch, hearing, incontinence, muscular dystrophy, cancer

AFM, patch clamp, optical microscopy, computing

GsMTx4

HEK, 3T3, COS, human bladder

HPLC, FPLC, fluorimetry, molecular biology, NMR

Arrhythmias, blood pressure, touch, hearing, incontinence, muscular dystrophy, cancer

C. Elegans, tarantulas, mice, rats; skeletal muscle, heart muscle

Meng, F., and F. Sachs. 2008. A molecular stress sensor for living cells. (submitted)

Pennell, T., J. Wang, T. Suchyna, J. Heo, J. D. Felske, F. Sachs, and S. Z. Hua. 2008. "A microfluidic chip to produce temperature jumps for electrophysiology" Analytical Chemistry in press.

Posokhov, Y. G., A. Freites, P. Gottlieb, F. Sachs, and A. S. Ladokhin. 2008. Experimental and Molecular Dynamics (MD) Characterization of Membrane Interactions of the Cysteine Knot (CK) Family of Ion-Channel Blockers Biophysical Journal.

Spagnoli, C., A. Beyder, S. Besch, and F. Sachs. 2008. AFM analysis of cell volume; the cell as a sponge Phys Rev E Stat Nonlin.Soft.Matter Phys.

Basak, S., A. Beyder, C. Spagnoli, A. Raman, and F. Sachs. 2007. Hydrodynamics of torsional probes for atomic force microscopy in liquids. Journal of Applied Physics 102:024914.

Bowman, C. L., P. A. Gottlieb, T. M. Suchyna, Y. K. Murphy, and F. Sachs. 2007. Mechanosensitive ion channels and the peptide inhibitor GsMTx-4: History, properties, mechanisms and pharmacology. Toxicon 49:249-270.

Chemin, J., A. J. Patel, F. Duprat, F. Sachs, M. Lazdunski, and E. Honore. 2007. Up- and down-regulation of the mechano-gated K-2P channel TREK-1 by PIP2 and other membrane phospholipids. Pflugers Archiv-European Journal of Physiology 455:97-103.

Chemin, J., F. Sachs, A. A. Patel, M. Lazdunski, and E. Honore. 2007. Polymodal regulation of the mechano-gated K 2P channel TREK-1 by PIP 2 and other membrane phospholipids. Current Topics in Membranes and Transport.

Gottlieb, P., R. Maroto, A. Raso, T. G. Wood, A. Kurosky, B. Martinac, O. Hamill, C. B. Bowman, J. H. A. Folgering, A. Patel, F. Sachs, and E. Honore. 2007. Revisiting TRPC1 mechanosensitivity Pflugers Arch.

Heo, J., F. Meng, F. Sachs, and S. Hua. 2007. Dynamic effects of Hg 2 induced change in cell volume.

Kockskamper, J., D. von Lewinski, M. Khafaga, A. Elgner, M. Grimm, T. Eschenhagen, F. Sachs, and B. Pieske. 2007. The slow force response to stretch in atrial and ventricular myocardium from human heart - functional relevance and subcellular mechanisms Progress in Biophysics and Molecular Biology.

Posokhov, Y. G., P. Gottlieb, M. Morales, F. Sachs, and A. S. Ladokhin. 2007. Is Lipid Bilayer Binding a Common Property of Inhibitor Cysteine Knot Ion-Channel Blockers? Biophys.J.

Posokhov, Y. O., J. A. Freites, P. A. Gottlieb, F. Sachs, D. J. Tobias, and A. S. Ladokhin. 2007. Experimental and molecular dynamics (MD) characterization of membrane interactions of the cysteine knot (CK) family of ion-channel blockers. Biophysical Journal:544A-545A.

Sachs, F. 2007. Lack of correlation between NIH funding and publication rate.

Suchyna, T., and F. Sachs. 2007. Mechanical and electrical properties of membranes from dystrophic and normal mouse muscle. J.Physiol.(Lond) 581:369-387.

Beyder, A., and F. Sachs. 2006. Microfabricated torsion levers optimized for low force and high-frequency operation in fluids. Ultramicroscopy 106:838-846.

Beyder, A., C. Spagnoli, and F. Sachs. 2006. Reducing probe dependent drift in atomic force microscope with symmetrically supported torsion levers. Review of Scientific Instruments 77.

Bowman, C., P. A. Gottlieb, T. Suchyna, Y. K. Murphy, and F. Sachs. 2006. Mechanosensitive Ion Channels and the Peptide Inhibitor GsMTx4: History, Properties, Mechanisms and Pharmacology. Toxicon.

Honore, E., A. A. Patel, T. Suchyna, and F. Sachs. 2006. Inactivation of mechanosensitive 2P domain ion channels. Biophys.J.:1543 Plat.

Jacques-Fricke, B. T., Y. Seow, P. A. Gottlieb, F. Sachs, and T. M. Gomez. 2006. Ca2 influx through mechanosensitive channels inhibits neurite outgrowth in opposition to other influx pathways and release from intracellular stores. J.Neurosci. 26.

Markin, V., and F. Sachs. 2006. Thermodynamics of mechanosensitivity. Current Topics in Membranes and Transport.

Milescu, L. S., A. Yildiz, P. R. Selvin, and F. Sachs. 2006. Extracting dwell time sequences from processive molecular motor data. Biophysical Journal 91:3135-3150.

Milescu, L. S., A. Yildiz, P. R. Selvin, and F. Sachs. 2006. Maximum likelihood estimation of molecular motor kinetics from staircase dwell-time sequences. Biophysical Journal 91:1156-1168.

Sachs, F. 2006. Probing the Double Layer: Effect of Image Forces on AFM. Biophys J 91:L14-L15.

Ateya, D. A., F. Sachs, P. A. Gottlieb, S. Besch, and S. Z. Hua. 2005. Volume cytometry: Microfluidic sensor for high-throughput screening in real time. Analytical Chemistry 77:1290-1294.

Kohl, P., F. Sachs, and M. R. Franz. 2005. Cardiac Mechano-Electric Feedback and Arrhythmias; from pipette to patient. Elsevier, Philadelphia.

Milescu, L. S., G. Akk, and F. Sachs. 2005. Maximum likelihood estimation of ion channel kinetics from macroscopic currents. Biophysical Journal 88:2494-2515.

Ostrow, L., and F. Sachs. 2005. Mechanosensation and Endothelin in Astrocytes - potential roles in reactive gliosis. Brain Research Reviews 48:488-508.

Sachs, F., P. Kohl, and M. R. Franz. 2005. Stretch-activated channels in the heart. In Cardiac Mechano-Electric Feedback and Arrhythmias: From Pipette to Patient. Elsevier, Philadelphia. 2-11.

Suchyna, T., F. Sachs, P. Kohl, and M. R. Franz. 2005. Membrane/Cytoskeleton Interface and Mechanosensitive Channels. Elsevier, Philadelphia. 42-52.

Yeung, E. W., N. P. Whitehead, T. M. Suchyna, P. A. Gottlieb, F. Sachs, and D. G. Allen. 2005. Effects of stretch-activated channel blockers on [Ca2 ]i and muscle damage in the mdx mouse. Journal Of Physiology-London 562:367-380.

Bao, L., F. Sachs, and G. Dahl. 2004. Connexins are mechanosensitive. American Journal Of Physiology-Cell Physiology 287:C1389-C1395.

Gottlieb, P., T. Suchyna, and F. Sachs. 2004. Mechanosensitive Ion Channels as Drug Targets. Current Drug Targets - CNS & Neurological Disorders 3:287-295.