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Communication Dans Un Congrès Année : 2013

Real time biomechanical characterization of DNA damage under therapeutic radiation beams

Thomas Lacornerie
  • Fonction : Auteur
Momoko Kumemura
Nicolas Lafitte
  • Fonction : Auteur
Laurent Jalabert
  • Fonction : Auteur
  • PersonId : 1150449
Eric Lartigau
  • Fonction : Auteur
Teruo Fuji
  • Fonction : Auteur
Hiroyuki Fujita
  • Fonction : Auteur
Dominique Collard

Résumé

We report the first, real-time biomechanical measurement of a DNA bundle degradation in solution when exposed to a therapeutic radiation beam. The Silicon Nano Tweezers and their microfluidic housing endure the harsh environment of radiation beams and still retain molecular-level accuracy. This result paves the way for both fundamental and clinical studies of DNA degradation under radiation for improved cancer treatment. Tumor cell killing by γ-ray beams in cancer radiotherapy is currently based on a rather empirical understanding of the basic mechanisms and effectiveness of DNA damage by radiation. On the other hand, the mechanical behavior of DNA, e.g., sequence-sensitivity, elastic vs. elastic response, is well understood. However, manipulations are usually performed by AFM or optical tweezers, instruments that can hardly be placed and operate under radiation beams. The Silicon Nano Tweezers (SNT) is a MEMS device for direct manipulation of biomolecules, an excellent candidate for in-beam operation thanks to its tiny size. The SNT comprise two parallel arms ending with sharp tips, designed to trap molecules by dielectrophoresis. The mobile arm is displaced by an electrostatic actuator. The motion is acquired by a position sensor, thus the mechanical characteristic of the trapped molecules (stiffness, viscosity) are measured in real time. SNT's tips are placed inside a microfluidic cavity; the alignment and the insertion are controlled by a micro-robot. The experiments are performed with a Cyberknife, a LINAC accelerator mounted on a robot arm, at the Department of Radiation Therapy of Centre Oscar Lambret. The SNT inside a microfluidic cavity is placed under the Cyberknife. The collimated beam, delivering an intense 6 MeV photon flux, completely encompasses the SNT holding the DNA bundle in the microfluidic cavity. We are working on a combined multiscale simulation scheme, ranging from molecular dynamics to Monte Carlo to continuum mechanics, which will ultimately enable to correlate the macroscopic response to the underlying molecular damage. Silicon Nanotweezers operation under therapeutic irradiation and direct detection of DNA damage under γ-ray beam was first demonstrated. Coupled with microfluidics, and in the future with biological assay technology, this new capability permits to study the mechanics of DNA damage under ionizing beams for optimized and patient-specific cancer treatments.
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Dates et versions

hal-00944021 , version 1 (11-02-2014)

Identifiants

  • HAL Id : hal-00944021 , version 1

Citer

Gregoire Perret, Thomas Lacornerie, Momoko Kumemura, Nicolas Lafitte, Hervé Guillou, et al.. Real time biomechanical characterization of DNA damage under therapeutic radiation beams. Materials Research Society Fall Meeting, MRS Fall 2013, Symposium I : Multiscale Materials in the Study and Treatment of Cancer, 2013, Boston, MA, United States. ⟨hal-00944021⟩
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