Computational biophysics of atomic force microscopy—an IUPAB-sponsored workshop

Abstract

Atomic Force Microscopy (AFM) is a structural determination technique that involves ‘prodding’ surfaces with a nanometer sized needle with concomitant measurement of the resisting force. Due to its ability to interrogate the nanometer-to-micrometer size range, AFM is especially suited to the structural analysis of everything from biopolymers to cells and, as such, has become an important biophysical method. As AFM was only invented in 1986 it is relatively less scientifically developed than other structural techniques, such as NMR, X-ray crystallography and electron microscopy, that have a longer history of usage. In September of 2022 the first workshop of its kind was held to examine modern computational methods useful for simulating and analysing bioAFM experiments. Sponsored by a small IUPAB workshop grant, the three day meeting was of the hybrid (joint online /in person) type and had presenting participants based in Australia, UK, Finland, Thailand, South Korea, Vietnam and Japan. Each invited speaker was asked to deliver a lecture composed of half educational material (pitched at the level of an advanced postgraduate student) and half cutting edge research material (gathered from their own studies). IUPAB funds were used to invite young researchers (postgraduate students and early career scientists) from both within Japan and countries in the near asian region who had an interest in learning about the theoretical and experimental basis of the AFM technique. This Editorial describes the workshop and introduces the written contributions from the invited lecturers.

Introduction

The historical city of Kanazawa, sometimes called “Little Kyoto,” was the venue for a recent IUPAB-sponsored workshop on the computational biophysics of atomic force microscopy (Fig. 1). Aside from having spectacular natural beauty (mountains next to the ocean), an ancient castle (Kanazawa-jo) and perhaps the most beautiful and famous historical garden in Japan (Kenrokuen), the city of Kanazawa is also famous for housing one of Japan’s 14 world premier institutes (WPIs) which are special centers of science and technology, dedicated to a single topic, that receive high levels of  research funding and support from the Japanese government. The center based in Kanazawa city, known as the WPI-Nano Life Science Institute (Nano-LSI), is housed in the mountainous Kakuma campus of Kanazawa University. Built around the ground-breaking achievements of Prof. Toshio Ando, the major focus of the WPI-Nano LSI is the development and application of scanning probe microscopy (SPM) procedures, such as atomic force microscopy (AFM) and scanning ion conductance microscopy (SICM), to the analysis and interrogation of biological processes occurring at the nano- to meso-scale (e.g., from atomic structure to analysis of the behavior and properties of cells and tissues). One of the four sections of the Nano-LSI is devoted to the application of computational science to outstanding problems in SPM and it was the members of this group that organized the workshop.

Fig. 1

A collage of images associated with the IUPAB Workshop on the Computational Biophysics of Atomic Force Microscopy. (Top Left) Poster advertising the event with the list of scientific and non-scientific speakers. (Top Right) The three organizers of the event (Takashi Sumikama (left in picture), Holger Flechsig (right in picture) and Damien Hall (center)) at an early planning session. (Center Right) The WPI-NanoLSI building at Kanazawa University at which the event was held. (Bottom) Various photographs of the 3-day event showing speakers, travel award recipients, and meeting attendees. Further details about the event can be read at the following web page: https://nanolsi.kanazawa-u.ac.jp/en/news/23751

The workshop was conducted over three days and involved 22 scientific talks (of 30-min to 1-h duration) delivered by speakers based in Japan, UK, Finland, and Australia (Table 1). Talks were divided into five sessions and dealt with subject areas ranging from software development for machine control, in silico-based experimental parameter optimization, simulation of SPM experiments by approaches using coarse-grained to quantum levels of detail, machine learning methodology, post-acquisition structural data analysis, and theoretical methods for calculating the statistics of single-molecule experiments. The workshop had 244 registrants with 36 onsite attendees and 67 online multi-user zoom channels opened in 23 different countries. IUPAB funds were used to sponsor 8 travel awards, with three international awards provided to participants from the near Asia region and five domestic awards given to participants from the five different regions of Japan (Table 2). The aim of the workshop was to introduce a wide range of computational and theoretical methods applicable to both simulating and analysing SPM experiments and, in this, it was successful.

Table 1 Scientific talks—invited lecturer and seminar title

Table 2 Recipients of international and domestic travel IUPAB awards

Contents of this issue focus

At the beginning of 2023, a personal invitation was sent to all invited speakers and eight travel awardees to contribute either a review article or a short letter describing the scientific background of their lecture or poster presentations. Further to these direct invitations, an open call was published in the February 2023 edition of Biophysical Reviews (Sumikama et al. 2023) requesting any interested scientists to participate in a focused collection dedicated to the topic of the computational biophysics of AFM. In total, this call resulted in five accepted articles that together form the basis of this Issue Focus (Table 3). In this section, we provide a brief summary of each contribution.

Table 3 Articles appearing in this Issue Focus

Directly following the Issue Focus Editorial (Hall et al. 2023) is a contribution from Fukuda and Ando that describes the physical basis and relevant engineering control theory behind the operation of modern high-speed AFM devices (Fukuda and Ando 2023). This authorship team pairs Toshio Ando (one of the original developers of the high-speed AFM technique (e.g. see Ando 2022)) with Shingo Fukuda (a young engineering Assistant Professor developing the next generation of high-speed AFM devices (see Fukuda and Ando 2021)) with the result that the review provides both an excellent historical overview and a clear identification of the major obstacles to future progress in the generation of ever higher speed AFM devices (Fukuda and Ando 2023). The next article is a Letter contributed by Dr. George Heath summarizing recent developments in the application of information theory to the analysis of AFM images (Heath 2023). Dr. Heath is one of the world leaders in this field having recently developed a structure determination technique of sub-pixel super-resolution analysis known as Localization Atomic Force Microscopy (Heath et al. 2021). The fourth contribution to this Issue Focus was made by Takashi Sumikama—a theoretical chemist investigating the behavior of large protein assembles and membrane transporters using simulation approaches (Sumikama 2023). In his short Letter, Sumikama describes recent work using coarse to intermediate-grained molecular dynamics simulations to directly examine the forces governing the interaction between the AFM probe and a simplified polymer representation of condensed chromosomes—with these simulations used to help understand the results of 3D AFM experiments (Sumikama 2023; Sumikama et al. 2022). The final contribution to this Issue Focus is a short Letter describing recently developed software approaches for simulating and optimizing HSAFM experiments when the biological surface is highly dynamic and or unstable over time (Hall 2023a). Known as HSAFM-UGOKU and HSAFM-MIREBA, these software tools are capable of providing information on linear reporting regimes and also generate the most likely forms of image distortion in virtual AFM experiments (Hall and Foster 2022; Hall 2023a, b).

Concluding remarks

A great deal was learnt and, given the circumstances, a respectable amount of fun was had at this IUPAB-sponsored workshop on the topic of the computational biophysics of atomic force microscopy. Conducted during a period of re-opening of Japanese society after a long time of COVID-related closure, the workshop allowed for new contacts and friendships to be made and a lot of healthy scientific discussion to be entered into. The three organizers of the event (Takashi Sumikama, Holger Flechsig and Damien Hall) would like to thank both the staff of the NanoLSI and IUPAB for the award of a small workshop grant that allowed this event to be realized.