Single Molecule Studies Enabled by Model-Based Controller Design

• Published in: IEEE/ASME transactions on mechatronics 2018-08, Vol.23 (4), p.1532-1542
• Main Authors: Bhaban, Shreyas, Talukdar, Saurav, Li, Mingang, Hays, Thomas, Seiler, Peter, Salapaka, Murti
• Format: Article
• Language: English
• Subjects: Acousto-optic deflector (AOD); Adaptive optics; Charge carrier processes; Computer simulation; Control systems design; Design optimization; Force; intracellular transport; kinesin motility assay; Laser beams; mixed objective <inline-formula xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"> <tex-math notation="LaTeX"> H_2/H_\infty</tex-math> </inline-formula> optimization; molecular motor proteins; Molecular motors; Motion simulation; optical force clamp; Optical sensors; optical trapping; Proteins; Real time; Statistical analysis; Statistical methods; system identification; Thermal noise; Ultrafast optics
• ISSN: 1083-4435; 1941-014X
• DOI: 10.1109/TMECH.2018.2852367

Optical tweezers have enabled important insights into intracellular transport through the investigation of motor proteins, with their ability to manipulate particles at the microscale, affording femto newton force resolution. Its use to realize a constant force clamp has enabled vital insights into the behavior of motor proteins under different load conditions. However, the varying nature of disturbances and the effect of thermal noise pose key challenges to force regulation. Furthermore, often the main aim of many studies is to determine the motion of the motor and the statistics related to the motion, which can be at odds with the force regulation objective. In this paper, we propose a mixed objective H 2 /H ∞ optimization framework using a model-based design, that achieves the dual goals of force regulation and real-time motion estimation with quantifiable guarantees. Here, we minimize the H ∞ norm for the force regulation and error in step estimation while maintaining the H 2 norm of the noise on step estimate within user specified bounds. We demonstrate the efficacy of the framework through extensive simulations and an experimental implementation using an optical tweezer setup with live samples of the motor protein "kinesin", where regulation of forces below 1 piconewton with errors below 10% is obtained while simultaneously providing real-time estimates of motor motion.